{"gene":"LAMC2","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":1994,"finding":"Loss-of-function mutations (premature stop codons) in LAMC2, encoding the γ2 subunit of laminin-5 (nicein/kalinin), cause Herlitz junctional epidermolysis bullosa, establishing that LAMC2 is required for structural integrity of the cutaneous basement membrane zone.","method":"Genetic linkage analysis, microsatellite mapping, mutation identification by sequencing in H-JEB kindreds","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — independently replicated in two simultaneous papers (PMID 8012394 and 8012393), with multiple kindreds and mutation types confirming causal loss-of-function","pmids":["8012394","8012393"],"is_preprint":false},{"year":1996,"finding":"The LAMC2 gene contains 23 exons spanning 55 kb, and alternative splicing at the last exon produces two transcripts: the longer γ2 chain (exon 23) expressed broadly in epithelial tissues, and a shorter γ2* chain (using part of intron 22) expressed specifically in cerebral cortex, lung, and kidney distal tubules.","method":"Genomic library cloning, exon mapping, Northern hybridization of human embryonic tissues, cDNA analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genomic and expression analysis with tissue-specific validation, single lab","pmids":["8786121"],"is_preprint":false},{"year":1995,"finding":"TGF-β differentially enhances LAMC2, LAMA3, and LAMB3 gene expression in epidermal keratinocytes (greater effect on LAMA3 and LAMC2 than LAMB3); TNF-α alone does not alter LAMB3 or LAMC2 expression, indicating non-coordinate cytokine regulation of laminin-5 subunit genes.","method":"Northern hybridization with specific cDNA probes in primary keratinocytes and keratinocyte cell lines treated with TGF-β and TNF-α","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cytokine treatment with Northern blot in multiple cell types, single lab","pmids":["7635220"],"is_preprint":false},{"year":1999,"finding":"Intact laminin-5 promotes cell adhesion but recombinant γ2 chain alone does not, indicating the γ2 chain lacks an autonomous cell-binding site. However, antibodies against the short arm of the γ2 chain inhibited carcinoma cell migration in vitro, implicating the γ2 chain in cell locomotion. A cis-acting element between −613 and +55 of the LAMC2 promoter drives expression specifically in migratory epithelial cells of healing wounds in transgenic mice.","method":"Cell adhesion assay with purified laminin-5 and recombinant γ2, antibody blocking migration assay, promoter-lacZ reporter transgenic mice","journal":"Matrix biology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro reconstitution with antibody blocking, validated in transgenic reporter mice in vivo, multiple orthogonal methods in one study","pmids":["10372560"],"is_preprint":false},{"year":2001,"finding":"Integrity of the γ2 chain C-terminal amino acid sequences (domains I and II) is required for laminin-5 assembly: a truncating mutation in the terminal exon (γ2t) abolished laminin-5 assembly and deposition, whereas an in-frame deletion in domain V (γ2Δ4) still allowed assembly, secretion, and extracellular processing of laminin-5. This correlates a specific domain function with a mild versus severe JEB phenotype.","method":"Transfection of mutant γ2 cDNAs into γ2-null keratinocytes, immunofluorescence detection of laminin-5 deposition, patient mutation characterization","journal":"The Journal of investigative dermatology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstitution in null cells with domain-specific mutants establishing structure-function relationships, single lab but multiple orthogonal approaches","pmids":["11564184"],"is_preprint":false},{"year":2003,"finding":"TGF-β1 and HGF synergistically activate the LAMC2 promoter and induce laminin γ2 chain accumulation in colon carcinoma cells; this synergy requires the 5′ AP-1 element and an additional upstream element responsive to Smad3. The synergistic activation is specific to LAMC2 (not LAMA3 or LAMB3), explaining why γ2 chain accumulates at the invasive front of colon carcinomas.","method":"Promoter-reporter assays, Smad3 co-expression, cytokine treatment of colon carcinoma cell lines","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — promoter dissection with defined elements and transcription factor identification, single lab","pmids":["12519076"],"is_preprint":false},{"year":2013,"finding":"LAMC2 physically binds to EGFR in anaplastic thyroid carcinoma cells (shown by immunoprecipitation); silencing LAMC2 partially blocks EGF-mediated EGFR activation and downstream signaling, and EGFR blocking (cetuximab or siRNA) additively enhances antiproliferative effects of LAMC2 knockdown.","method":"shRNA knockdown, immunoprecipitation, Western blot for EGFR pathway activation, xenograft mouse model, rescue overexpression experiments","journal":"The Journal of clinical endocrinology and metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional epistasis in vitro and in vivo, single lab","pmids":["24170107"],"is_preprint":false},{"year":2015,"finding":"LAMC2 promotes lung adenocarcinoma migration and invasion via EMT in an integrin β1- and ZEB1-dependent manner; LAMC2 knockdown decreases traction force, migration, and invasion with reduction of EMT markers, and attenuates metastasis in mice.","method":"Genome-wide transcriptional analysis, shRNA knockdown, traction force microscopy, in vitro migration/invasion assays, mouse metastasis model","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional KD with defined pathway placement (integrin β1/ZEB1), in vivo validation, single lab","pmids":["25591736"],"is_preprint":false},{"year":2011,"finding":"LAMB3 and LAMC2 are upregulated in gastric cancer via promoter demethylation; DNA hypomethylation correlates with gene expression, and methylation inhibitor treatment induces their expression. ChIP demonstrates enrichment of the activation histone mark H3K4me3 at both gene promoters in expressing cells.","method":"DNA methylation analysis, gene expression profiling, methylation inhibitor treatment, chromatin immunoprecipitation (ChIP)","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epigenetic mechanism established by ChIP and inhibitor treatment, single lab","pmids":["21345334"],"is_preprint":false},{"year":2017,"finding":"Overexpression of LAMC2 (a target of miR-622) in gastric cancer cells activates the EGFR/ERK1/2-MMP7 signaling pathway, promoting cell invasion; this is shown by upregulation of phospho-EGFR, phospho-ERK1/2, and MMP7 upon LAMC2 overexpression and knockdown of CD82.","method":"LAMC2 overexpression and knockdown, Western blot for signaling proteins, cell invasion assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined pathway activation with gain/loss of function, single lab","pmids":["28252644"],"is_preprint":false},{"year":2019,"finding":"Silencing LAMC2 in cholangiocarcinoma cells suppresses EGFR signaling pathway activity, inhibiting EMT and cell invasion/migration in vitro and reducing angiogenesis (microvessel density) in vivo. The interaction between LAMC2 and EGFR signaling was confirmed: LAMC2 overexpression activates the EGFR pathway and EMT, whereas EGFR pathway inhibition phenocopies LAMC2 silencing.","method":"LAMC2 siRNA knockdown and overexpression, EGFR inhibitor treatment, EMT marker analysis, xenograft angiogenesis assay","journal":"The American journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal gain/loss of function with pathway inhibition epistasis, in vivo validation, single lab","pmids":["31345467"],"is_preprint":false},{"year":2020,"finding":"LAMC2 promotes pancreatic cancer cell migration and invasion by phosphorylating AKT-Ser473, which enhances expression, activity, and cell-membrane accumulation of NHE1 (sodium/hydrogen exchanger 1), generating extracellular acidification; this promotes actin-dependent pseudopodial formation and EMT.","method":"LAMC2 knockdown/overexpression, Western blot for AKT phosphorylation and NHE1, extracellular pH measurement, confocal microscopy of actin/NHE1 localization","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined AKT-NHE1 signaling axis with functional readouts, single lab, multiple methods","pmids":["32246993"],"is_preprint":false},{"year":2021,"finding":"LAMC2-null intrahepatic cholangiocarcinoma cells fail to induce EMT, migration, and invasion in hepatocellular carcinoma cells (conditioned medium experiments), demonstrating that secreted LAMC2 from cholangiocarcinoma cells acts in a paracrine manner to promote EMT of neighboring hepatocellular carcinoma cells.","method":"LAMC2 knockout (established LAMC2-KO cells), conditioned medium transfer, EMT marker analysis, migration/invasion assays","journal":"Journal of Cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO rescue experiment demonstrating paracrine mechanism, single lab","pmids":["33995623"],"is_preprint":false},{"year":2021,"finding":"A chromosomal translocation between LAMC2 (chr1) and NR6A1 (chr9) in ovarian cancer SKOV3 cells generates a novel fusion protein (Lm-γ2F) lacking domains I and II but retaining the EGF-like domain III (DIII). This truncated form is secreted and acts as an EGFR ligand activating EGFR/AKT pathways more effectively than full-length Lm-γ2, promoting proliferation, survival, and motility of ovarian cancer cells.","method":"In situ hybridization, RT-PCR of fusion transcripts, overexpression and suppression of fusion transcripts, Western blot for EGFR/AKT signaling, mouse xenograft tumor growth assays","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — novel mechanism with gain/loss of function, in vivo validation, single lab","pmids":["34689384"],"is_preprint":false},{"year":2023,"finding":"LAMC2 is localized in the endoplasmic reticulum (ER) of lung, breast, and liver cancer cells. Under ER stress, LAMC2 forms protein complexes with MYH9 and MYH10 to promote mitochondrial aggregation and enhanced ER-mitochondria interaction at the perinuclear region, attenuating ER stress, elevating mitochondrial membrane potential, and reducing ROS and apoptosis.","method":"Subcellular fractionation, co-immunoprecipitation of LAMC2 with MYH9/MYH10, tunicamycin-induced ER stress, mitochondrial membrane potential assays, ROS measurement, in vivo xenograft","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP defining protein complex, localization experiments with functional consequence, in vivo validation, single lab","pmids":["37891404"],"is_preprint":false},{"year":2023,"finding":"LAMC2 co-localizes with EGFR at the ER membrane; both the EGF-Lam and LamB domains of LAMC2 are required for EGFR binding. LAMC2 overexpression enhances EGFR membrane deposition and promotes EGFR transport from the ER, and LAMC2 prevents EGFR protein degradation via ubiquitination, thereby stabilizing EGFR expression.","method":"Deletion mutagenesis of LAMC2 domains, co-localization confocal imaging, EGFR membrane fractionation, ubiquitination assays, in vivo tumor growth","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion mutagenesis with functional readouts, multiple methods, single lab","pmids":["37542131"],"is_preprint":false},{"year":2023,"finding":"LAMC2 inhibition in pancreatic cancer impairs cell cycle and induces apoptosis; LAMC2 regulates a FOSL1-AXL axis via AKT phosphorylation, and genetic LAMC2 or pharmacological AXL inhibition shows synergistic antiproliferative effect with MEK1/2 inhibitors in 2D, 3D, and patient-derived organoid PDAC models.","method":"shRNA knockdown, RNA-sequencing, AKT phosphorylation assays, AXL inhibition, combination drug assays in 2D/3D/organoids and xenograft/allograft in vivo models","journal":"Clinical cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — transcriptional network defined by RNA-seq with functional validation across multiple model systems, single lab","pmids":["36607777"],"is_preprint":false},{"year":2022,"finding":"The transcription factor PATZ1, regulated downstream of RRP15, directly controls LAMC2 (and LAMB3) expression; loss of RRP15 reduces PATZ1 protein, decreasing LAMC2/LAMB3, which in turn suppresses the integrin β4 (ITGB4)/FAK/NF-κB signaling pathway and inhibits HCC cell migration.","method":"RRP15 knockdown, Western blot for PATZ1 and LAMC2, cell migration/invasion assays, in vivo mouse model","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined upstream regulator-transcription factor-LAMC2 axis with in vivo validation, single lab","pmids":["38475740"],"is_preprint":false},{"year":2024,"finding":"LAMC2 expression is induced by canonical TGF-β/SMAD2 signaling; in turn, LAMC2 feeds back to enhance TGF-β signaling by binding to TGF-β receptor II (TGF-βRII), forming a positive feedback loop that promotes gallbladder carcinoma EMT and metastasis.","method":"Western blot, RT-qPCR, TGF-β/SMAD2 pathway inhibition, LAMC2 silencing, in vivo metastasis model, organoid assays","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — bidirectional pathway relationship established with gain/loss of function and in vivo validation, single lab","pmids":["41392239"],"is_preprint":false},{"year":2024,"finding":"NSUN2, an m5C methyltransferase, promotes LAMC2 mRNA stability through m5C modification in an YBX1-dependent manner; NSUN2 knockdown reduces m5C modification at LAMC2 and decreases LAMC2 expression, suppressing EMT and tumor progression in head and neck squamous cell carcinoma.","method":"m5C-Bis-Seq (transcriptome-wide m5C profiling), NSUN2 knockdown, in vitro and in vivo functional assays","journal":"Biomedicines","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — transcriptome-wide m5C mapping identifies LAMC2 as target, single lab","pmids":["39595099"],"is_preprint":false},{"year":2024,"finding":"Hypoxia induces global histone lactylation and specifically increases H3K9 lactylation (H3K9la) at the LAMC2 promoter, enhancing LAMC2 transcription and promoting ESCC invasion.","method":"Quantitative proteomics of histone modifications, MNase ChIP-seq for H3K9la, RNA-seq, in vitro and in vivo ESCC models","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq demonstrates H3K9la enrichment at LAMC2 promoter with functional consequence, single lab","pmids":["38989468"],"is_preprint":false},{"year":2024,"finding":"LAMC2 promotes trophoblast invasion via the PI3K/Akt/MMP2/MMP9 signaling pathway: LAMC2 overexpression elevates phospho-Akt, MMP2, and MMP9 protein levels and increases invasion/migration; PI3K inhibitor LY294002 abolishes these effects.","method":"LAMC2 overexpression/knockdown in HTR8/SVneo cells, Western blot for PI3K/Akt/MMP2/9, invasion/migration assays, PI3K inhibitor treatment","journal":"The journal of obstetrics and gynaecology research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pathway inhibitor epistasis with gain/loss of function, single lab","pmids":["36412218"],"is_preprint":false},{"year":2024,"finding":"LAMC2 promotes TNBC proliferation and migration by upregulating CD44 and activating STAT3 signaling; luciferase reporter assays showed LAMC2 targets the ZEB1 promoter to drive its transcription.","method":"Luciferase reporter assay (ZEB1 promoter), Western blot for CD44/STAT3, cell viability and migration assays, xenograft mouse model","journal":"Molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase assay defining transcriptional target with in vivo validation, single lab","pmids":["38760717"],"is_preprint":false},{"year":2025,"finding":"GSDMD binds LAMC2 directly and induces its ubiquitin-mediated proteasomal degradation; GSDMD deficiency stabilizes LAMC2, driving M2 macrophage polarization and CXCL5 secretion, which activates the AKT/NF-κB axis and suppresses cytotoxic T lymphocyte activity in prostate cancer.","method":"GSDMD deletion models, protein interaction analysis (co-IP), ubiquitination assays, immune cell profiling, correlative analysis in human PCa samples","journal":"Journal for immunotherapy of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — protein interaction and ubiquitination mechanism identified with in vivo immune profiling, single lab","pmids":["42203263"],"is_preprint":false},{"year":2025,"finding":"ODAPH physically interacts with LAMC2 (confirmed by co-immunoprecipitation) and activates the LAMC2/ITGB6/TGF-β1/ALP signaling axis to promote ameloblast adhesion and mineralization; integrin inhibition (CWHM-12) abrogates ODAPH-mediated TGF-β1/ALP induction.","method":"Co-immunoprecipitation, ODAPH overexpression, integrin inhibitor treatment, Western blot for pathway proteins, ALP activity assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP confirming interaction, inhibitor epistasis defining signaling axis, single lab","pmids":["40680053"],"is_preprint":false},{"year":2021,"finding":"LAMC2 promotes gemcitabine resistance in pancreatic cancer via upregulation of ATP-binding cassette (ABC) transporters and regulation of EMT; LAMC2 knockdown enhances gemcitabine sensitivity and apoptosis in PC cell lines.","method":"siRNA knockdown, cell viability and apoptosis assays, gene expression correlation of ABC transporters","journal":"Carcinogenesis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional KD with defined molecular correlate (ABC transporters) but mechanistic link is correlational, single lab","pmids":["33624791"],"is_preprint":false},{"year":2020,"finding":"miR-146a directly targets LAMC2 (validated by dual-luciferase reporter assay) to suppress the PI3K/Akt signaling pathway, increasing chemosensitivity of ovarian cancer cells to docetaxel/taxane; hUCMSC-derived exosomes delivering miR-146a reduce OC cell growth and resistance via this LAMC2-PI3K/Akt axis.","method":"StarBase/miRSearch database prediction, dual-luciferase reporter assay, miR-146a inhibitor transfection, LAMC2 overexpression, PI3K/Akt Western blot","journal":"International journal of molecular medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — luciferase validation of miR target site plus pathway assays, single lab, no direct LAMC2 domain or protein mechanism","pmids":["32626953"],"is_preprint":false},{"year":2001,"finding":"Mouse Lamc2 generates a smaller mRNA isoform via an alternative transcriptional start site within exon 19 (with promoter activity confirmed by reporter assay) and an alternatively spliced exon 19B containing stop codons, revealing distinct mechanisms of alternative mRNA generation between mouse and human LAMC2.","method":"5′ RACE, primer extension, genomic DNA analysis, alkaline phosphatase reporter assay","journal":"Molecules and cells","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, promoter reporter assay plus RACE, no functional consequence of isoform defined","pmids":["11804339"],"is_preprint":false}],"current_model":"LAMC2 encodes the γ2 chain of laminin-5 (laminin-332), which is essential for basement membrane structural integrity (loss-of-function mutations cause junctional epidermolysis bullosa); the γ2 chain's C-terminal domains are required for laminin-5 heterotrimer assembly and secretion, while its EGF-like domain III can act as an EGFR ligand. In cancer cells, LAMC2 localizes at the ER where it binds EGFR to promote its membrane transport and prevent ubiquitin-mediated degradation; LAMC2 also forms complexes with MYH9/MYH10 at ER-mitochondria contact sites to attenuate ER stress. Extracellularly, LAMC2 drives EMT, migration, and invasion through multiple downstream pathways including integrin β1/ZEB1, EGFR/ERK/MMP7, AKT/NHE1-mediated extracellular acidification, PI3K/AKT/MMP2/9, FOSL1-AXL/AKT, and CD44/STAT3/ZEB1; its transcription is induced by TGF-β/SMAD2/AP-1 and HGF synergy via defined promoter elements, and epigenetically regulated by promoter demethylation, H3K9 lactylation under hypoxia, and NSUN2-mediated m5C mRNA stabilization. GSDMD antagonizes LAMC2 function by inducing its ubiquitin-mediated proteasomal degradation, preventing M2 macrophage polarization."},"narrative":{"mechanistic_narrative":"LAMC2 encodes the γ2 chain of laminin-5 (laminin-332), a basement membrane glycoprotein whose loss-of-function mutations cause Herlitz junctional epidermolysis bullosa, establishing its essential role in cutaneous basement membrane integrity [PMID:8012394, PMID:8012393]. Assembly of the laminin-5 heterotrimer requires the integrity of the γ2 C-terminal domains (I and II); a terminal-exon truncation abolishes assembly and deposition, whereas a domain V in-frame deletion permits secretion and processing, correlating domain function with disease severity [PMID:11564184]. The isolated γ2 chain lacks an autonomous cell-binding site, yet antibodies against its short arm block carcinoma cell migration, and a defined promoter element drives expression in migratory epithelial cells of healing wounds [PMID:10372560]. Beyond its structural role, LAMC2 acts as a potent driver of epithelial-mesenchymal transition, migration, and invasion across many carcinomas, signaling through integrin β1/ZEB1 [PMID:25591736], EGFR/ERK/MMP7 [PMID:28252644], AKT-driven NHE1 extracellular acidification [PMID:32246993], PI3K/AKT/MMP2/9 [PMID:36412218], FOSL1-AXL/AKT [PMID:36607777], and CD44/STAT3/ZEB1 with direct transcriptional activation of ZEB1 [PMID:38760717], and it can act in a paracrine manner via secretion [PMID:33995623]. A central function is regulation of EGFR: LAMC2 localizes to the endoplasmic reticulum where it binds EGFR via its EGF-Lam and LamB domains, promoting EGFR membrane transport and preventing its ubiquitin-mediated degradation [PMID:37542131], and a LAMC2-NR6A1 fusion retaining the EGF-like domain III acts as a secreted EGFR ligand [PMID:34689384]. At the ER, LAMC2 also complexes with MYH9/MYH10 to enhance ER-mitochondria contact and attenuate ER stress and apoptosis [PMID:37891404]. Its transcription is induced by TGF-β/SMAD signaling—including a TGF-βRII positive-feedback loop [PMID:41392239]—synergizing with HGF via AP-1 and Smad-responsive promoter elements [PMID:12519076], and is epigenetically controlled by promoter demethylation [PMID:21345334], hypoxia-driven H3K9 lactylation [PMID:38989468], and NSUN2/YBX1-mediated m5C mRNA stabilization [PMID:39595099]. GSDMD antagonizes LAMC2 by inducing its ubiquitin-mediated proteasomal degradation, linking LAMC2 to M2 macrophage polarization and immune suppression [PMID:42203263].","teleology":[{"year":1994,"claim":"Established that LAMC2 is genetically required for basement membrane integrity by linking loss-of-function mutations to a heritable blistering disease.","evidence":"Genetic linkage and mutation sequencing in Herlitz junctional epidermolysis bullosa kindreds","pmids":["8012394","8012393"],"confidence":"High","gaps":["Did not define which γ2 domains mediate assembly versus secretion","No molecular mechanism for how γ2 loss destabilizes the basement membrane"]},{"year":1996,"claim":"Defined the LAMC2 gene structure and revealed tissue-specific alternative splicing generating a distinct γ2* transcript, raising the possibility of isoform-specific functions.","evidence":"Genomic cloning, exon mapping, and Northern hybridization of human embryonic tissues","pmids":["8786121"],"confidence":"Medium","gaps":["No functional role assigned to the γ2* isoform","Protein-level confirmation of the short isoform absent"]},{"year":1999,"claim":"Distinguished the γ2 chain's structural adhesion role from a migration-promoting role, showing it lacks an autonomous cell-binding site yet contributes to locomotion.","evidence":"Cell adhesion assays with recombinant γ2, antibody-blocking migration assays, and promoter-lacZ transgenic mice","pmids":["10372560"],"confidence":"High","gaps":["Molecular partner mediating migration not identified","Promoter element drivers (transcription factors) not yet defined"]},{"year":2001,"claim":"Mapped the γ2 C-terminal domains as the determinant of laminin-5 assembly, providing a structure-function basis for mild versus severe disease.","evidence":"Transfection of domain-specific mutant γ2 cDNAs into γ2-null keratinocytes with immunofluorescence of laminin-5 deposition","pmids":["11564184"],"confidence":"High","gaps":["Atomic structural model of the assembly interface lacking","How partial assembly translates to residual basement membrane function unresolved"]},{"year":2003,"claim":"Identified the transcriptional logic for LAMC2 overexpression at the invasive tumor front, showing TGF-β/HGF synergy acts specifically on the LAMC2 promoter.","evidence":"Promoter-reporter assays with Smad3 co-expression and cytokine treatment in colon carcinoma cells","pmids":["12519076","7635220"],"confidence":"Medium","gaps":["Did not establish the downstream invasive effectors","Specificity for LAMC2 over LAMA3/LAMB3 mechanism incompletely explained"]},{"year":2017,"claim":"Connected LAMC2 to oncogenic EGFR signaling, demonstrating physical binding to EGFR and pathway dependence in carcinoma.","evidence":"Co-immunoprecipitation, shRNA knockdown, EGFR pathway Western blots, and xenografts in thyroid and gastric cancer cells","pmids":["24170107","28252644"],"confidence":"Medium","gaps":["Binding interface and subcellular site of LAMC2-EGFR interaction not yet defined","Single Co-IP without reciprocal structural validation"]},{"year":2021,"claim":"Resolved multiple downstream invasion axes (integrin β1/ZEB1, AKT/NHE1 acidification, PI3K/AKT/MMP, FOSL1-AXL) and showed paracrine secreted LAMC2 drives EMT in neighboring cells.","evidence":"Knockdown/overexpression, traction force microscopy, extracellular pH measurement, conditioned-medium transfer, and metastasis models across lung, pancreatic, and cholangiocarcinoma","pmids":["25591736","32246993","33995623","36607777"],"confidence":"Medium","gaps":["Receptors mediating paracrine LAMC2 signaling not all identified","Relative contribution of each axis in vivo unclear"]},{"year":2023,"claim":"Reassigned a major LAMC2 function to intracellular ER compartments, where it stabilizes EGFR against degradation and engages MYH9/MYH10 to attenuate ER stress.","evidence":"Domain-deletion mutagenesis, subcellular fractionation, co-IP, ubiquitination assays, and mitochondrial/ROS readouts in lung, breast, and liver cancer cells","pmids":["37542131","37891404"],"confidence":"Medium","gaps":["How a secreted basement membrane protein is retained in the ER mechanistically unresolved","Identity of the EGFR E3 ligase that LAMC2 antagonizes unknown"]},{"year":2024,"claim":"Established multilayered upstream control of LAMC2, spanning a TGF-β receptor feedback loop, RRP15-PATZ1 transcription, hypoxic histone lactylation, and m5C mRNA stabilization.","evidence":"Pathway inhibition, ChIP-seq for H3K9la, m5C-Bis-Seq, luciferase reporters, and in vivo models across gallbladder, HCC, ESCC, HNSCC, and TNBC","pmids":["41392239","38475740","38989468","39595099","38760717"],"confidence":"Medium","gaps":["Hierarchy and crosstalk among these regulatory inputs not integrated","Cell-type specificity of each regulatory layer untested"]},{"year":2025,"claim":"Linked LAMC2 stability to immune evasion and to non-malignant adhesion/mineralization, showing GSDMD-driven degradation regulates macrophage polarization and an ODAPH-LAMC2-integrin axis governs ameloblast function.","evidence":"Co-IP, ubiquitination assays, and immune profiling in prostate cancer; co-IP and integrin inhibition in ameloblasts","pmids":["42203263","40680053"],"confidence":"Medium","gaps":["GSDMD-LAMC2 binding interface not mapped","Whether ER-resident versus secreted LAMC2 pools are differentially degraded unknown"]},{"year":null,"claim":"How LAMC2 partitions between its canonical secreted basement-membrane role and its non-canonical intracellular ER/EGFR-stabilizing role, and what governs this switch, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of LAMC2 in ER complexes","Mechanism retaining LAMC2 in the ER versus secreting it is undefined","Causal ordering between transcriptional, epigenetic, and post-translational controls not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,4]},{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[13]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[15,14]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[14,15]},{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[0,4]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[12,13]}],"pathway":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"complexes":["laminin-5 (laminin-332)"],"partners":["EGFR","MYH9","MYH10","TGFBR2","GSDMD","ODAPH","ITGB1","ITGB4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13753","full_name":"Laminin subunit gamma-2","aliases":["Cell-scattering factor 140 kDa subunit","CSF 140 kDa subunit","Epiligrin subunit gamma","Kalinin subunit gamma","Kalinin/nicein/epiligrin 100 kDa subunit","Ladsin 140 kDa subunit","Laminin B2t chain","Laminin-5 subunit gamma","Large adhesive scatter factor 140 kDa subunit","Nicein subunit gamma"],"length_aa":1193,"mass_kda":131.0,"function":"Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Ladsin exerts cell-scattering activity toward a wide variety of cells, including epithelial, endothelial, and fibroblastic cells","subcellular_location":"Secreted, extracellular space, extracellular matrix, basement membrane","url":"https://www.uniprot.org/uniprotkb/Q13753/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LAMC2","classification":"Not Classified","n_dependent_lines":10,"n_total_lines":1208,"dependency_fraction":0.008278145695364239},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/LAMC2","total_profiled":1310},"omim":[{"mim_id":"621324","title":"SECRETORY CALCIUM-BINDING PHOSPHOPROTEIN, PROLINE- AND GLUTAMINE-RICH, 1; SCPPPQ1","url":"https://www.omim.org/entry/621324"},{"mim_id":"619786","title":"EPIDERMOLYSIS BULLOSA, JUNCTIONAL 3B, SEVERE; JEB3B","url":"https://www.omim.org/entry/619786"},{"mim_id":"619785","title":"EPIDERMOLYSIS BULLOSA, JUNCTIONAL 3A, INTERMEDIATE; JEB3A","url":"https://www.omim.org/entry/619785"},{"mim_id":"608701","title":"NICOTINAMIDE NUCLEOTIDE ADENYLYLTRANSFERASE 2; NMNAT2","url":"https://www.omim.org/entry/608701"},{"mim_id":"605547","title":"FOLLISTATIN-LIKE 1; FSTL1","url":"https://www.omim.org/entry/605547"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"},{"location":"Golgi apparatus","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"urinary bladder","ntpm":36.5}],"url":"https://www.proteinatlas.org/search/LAMC2"},"hgnc":{"alias_symbol":["nicein-100kDa","kalinin-105kDa","BM600-100kDa"],"prev_symbol":["EBR2","LAMB2T","LAMNB2","EBR2A"]},"alphafold":{"accession":"Q13753","domains":[{"cath_id":"2.10.25.10","chopping":"38-141","consensus_level":"medium","plddt":82.0592,"start":38,"end":141},{"cath_id":"2.170.300.10","chopping":"142-187","consensus_level":"medium","plddt":90.9822,"start":142,"end":187},{"cath_id":"2.60.120.260","chopping":"204-379","consensus_level":"high","plddt":91.4297,"start":204,"end":379},{"cath_id":"-","chopping":"385-435","consensus_level":"medium","plddt":81.6418,"start":385,"end":435},{"cath_id":"1.10.287","chopping":"1071-1106_1121-1160","consensus_level":"medium","plddt":68.5701,"start":1071,"end":1160}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13753","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13753-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13753-F1-predicted_aligned_error_v6.png","plddt_mean":72.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LAMC2","jax_strain_url":"https://www.jax.org/strain/search?query=LAMC2"},"sequence":{"accession":"Q13753","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13753.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13753/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13753"}},"corpus_meta":[{"pmid":"8012394","id":"PMC_8012394","title":"Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5).","date":"1994","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8012394","citation_count":311,"is_preprint":false},{"pmid":"8012393","id":"PMC_8012393","title":"Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa.","date":"1994","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8012393","citation_count":264,"is_preprint":false},{"pmid":"29511340","id":"PMC_29511340","title":"LncRNA CASC9 promotes esophageal squamous cell carcinoma metastasis through upregulating LAMC2 expression by interacting with the CREB-binding protein.","date":"2018","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/29511340","citation_count":219,"is_preprint":false},{"pmid":"25591736","id":"PMC_25591736","title":"LAMC2 enhances the metastatic potential of lung adenocarcinoma.","date":"2015","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/25591736","citation_count":103,"is_preprint":false},{"pmid":"32626953","id":"PMC_32626953","title":"Exosomal microRNA‑146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2‑mediated PI3K/Akt axis.","date":"2020","source":"International journal of molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32626953","citation_count":78,"is_preprint":false},{"pmid":"24170107","id":"PMC_24170107","title":"Laminin-5γ-2 (LAMC2) is highly expressed in anaplastic thyroid carcinoma and is associated with tumor progression, migration, and invasion by modulating signaling of EGFR.","date":"2013","source":"The Journal of clinical endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/24170107","citation_count":68,"is_preprint":false},{"pmid":"33624791","id":"PMC_33624791","title":"LAMC2 promotes cancer progression and gemcitabine resistance through modulation of EMT and ATP-binding cassette transporters in pancreatic ductal adenocarcinoma.","date":"2021","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/33624791","citation_count":66,"is_preprint":false},{"pmid":"26905585","id":"PMC_26905585","title":"A functional polymorphism in lnc-LAMC2-1:1 confers risk of colorectal cancer by affecting miRNA binding.","date":"2016","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/26905585","citation_count":66,"is_preprint":false},{"pmid":"29315846","id":"PMC_29315846","title":"LINC00511 interacts with miR-765 and modulates tongue squamous cell carcinoma progression by targeting LAMC2.","date":"2018","source":"Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology","url":"https://pubmed.ncbi.nlm.nih.gov/29315846","citation_count":65,"is_preprint":false},{"pmid":"28252644","id":"PMC_28252644","title":"Nuclear Drosha enhances cell invasion via an EGFR-ERK1/2-MMP7 signaling pathway induced by dysregulated miRNA-622/197 and their targets LAMC2 and CD82 in gastric cancer.","date":"2017","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/28252644","citation_count":65,"is_preprint":false},{"pmid":"24976367","id":"PMC_24976367","title":"LAMC2 as a therapeutic target for cancers.","date":"2014","source":"Expert opinion on therapeutic targets","url":"https://pubmed.ncbi.nlm.nih.gov/24976367","citation_count":64,"is_preprint":false},{"pmid":"10372560","id":"PMC_10372560","title":"Laminin-5 promotes adhesion and migration of epithelial cells: identification of a migration-related element in the gamma2 chain gene (LAMC2) with activity in transgenic mice.","date":"1999","source":"Matrix biology : journal of the International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/10372560","citation_count":61,"is_preprint":false},{"pmid":"7635220","id":"PMC_7635220","title":"Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding the constitutive polypeptides, alpha 3, beta 3, and gamma 2, of human laminin 5 in epidermal keratinocytes.","date":"1995","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/7635220","citation_count":58,"is_preprint":false},{"pmid":"21345334","id":"PMC_21345334","title":"Aberrant up-regulation of LAMB3 and LAMC2 by promoter demethylation in gastric cancer.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/21345334","citation_count":56,"is_preprint":false},{"pmid":"38989468","id":"PMC_38989468","title":"Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma.","date":"2024","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/38989468","citation_count":48,"is_preprint":false},{"pmid":"36483681","id":"PMC_36483681","title":"Oral Cancer Stem Cell-Derived Small Extracellular Vesicles Promote M2 Macrophage Polarization and Suppress CD4+ T-Cell Activity by Transferring UCA1 and Targeting LAMC2.","date":"2022","source":"Stem cells international","url":"https://pubmed.ncbi.nlm.nih.gov/36483681","citation_count":47,"is_preprint":false},{"pmid":"36289544","id":"PMC_36289544","title":"LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer.","date":"2022","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/36289544","citation_count":42,"is_preprint":false},{"pmid":"32246993","id":"PMC_32246993","title":"LAMC2 modulates the acidity of microenvironments to promote invasion and migration of pancreatic cancer cells via regulating AKT-dependent NHE1 activity.","date":"2020","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/32246993","citation_count":39,"is_preprint":false},{"pmid":"8786121","id":"PMC_8786121","title":"Structure of the human laminin gamma 2 chain gene (LAMC2): alternative splicing with different tissue distribution of two transcripts.","date":"1996","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8786121","citation_count":39,"is_preprint":false},{"pmid":"31345467","id":"PMC_31345467","title":"Silencing of LAMC2 Reverses Epithelial-Mesenchymal Transition and Inhibits Angiogenesis in Cholangiocarcinoma via Inactivation of the Epidermal Growth Factor Receptor Signaling Pathway.","date":"2019","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/31345467","citation_count":38,"is_preprint":false},{"pmid":"12519076","id":"PMC_12519076","title":"Converging signals synergistically activate the LAMC2 promoter and lead to accumulation of the laminin gamma 2 chain in human colon carcinoma cells.","date":"2003","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/12519076","citation_count":35,"is_preprint":false},{"pmid":"19147813","id":"PMC_19147813","title":"Profiling bladder cancer organ site-specific metastasis identifies LAMC2 as a novel biomarker of hematogenous dissemination.","date":"2009","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/19147813","citation_count":34,"is_preprint":false},{"pmid":"12633536","id":"PMC_12633536","title":"A mutation in the LAMC2 gene causes the Herlitz junctional epidermolysis bullosa (H-JEB) in two French draft horse breeds.","date":"2003","source":"Genetics, selection, evolution : GSE","url":"https://pubmed.ncbi.nlm.nih.gov/12633536","citation_count":33,"is_preprint":false},{"pmid":"18559558","id":"PMC_18559558","title":"Overexpression of CDC25B and LAMC2 mRNA and protein in esophageal squamous cell carcinomas and premalignant lesions in subjects from a high-risk population in China.","date":"2008","source":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/18559558","citation_count":31,"is_preprint":false},{"pmid":"7861013","id":"PMC_7861013","title":"Identification of a homozygous exon-skipping mutation in the LAMC2 gene in a patient with Herlitz's junctional epidermolysis bullosa.","date":"1995","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/7861013","citation_count":31,"is_preprint":false},{"pmid":"27529842","id":"PMC_27529842","title":"LAMC2 is a predictive marker for the malignant progression of leukoplakia.","date":"2016","source":"Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology","url":"https://pubmed.ncbi.nlm.nih.gov/27529842","citation_count":29,"is_preprint":false},{"pmid":"34733944","id":"PMC_34733944","title":"LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer.","date":"2021","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34733944","citation_count":29,"is_preprint":false},{"pmid":"11564184","id":"PMC_11564184","title":"Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition.","date":"2001","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/11564184","citation_count":29,"is_preprint":false},{"pmid":"36607777","id":"PMC_36607777","title":"LAMC2 Regulates Key Transcriptional and Targetable Effectors to Support Pancreatic Cancer Growth.","date":"2023","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/36607777","citation_count":27,"is_preprint":false},{"pmid":"32568182","id":"PMC_32568182","title":"MicroRNA-134 inhibits tumor stem cell migration and invasion in oral squamous cell carcinomas via downregulation of PI3K-Akt signaling pathway by inhibiting LAMC2 expression.","date":"2020","source":"Cancer biomarkers : section A of Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/32568182","citation_count":27,"is_preprint":false},{"pmid":"31301414","id":"PMC_31301414","title":"LAMC2 regulated by microRNA-125a-5p accelerates the progression of ovarian cancer via activating p38 MAPK signalling.","date":"2019","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31301414","citation_count":26,"is_preprint":false},{"pmid":"9085255","id":"PMC_9085255","title":"Detection of novel LAMC2 mutations in Herlitz junctional epidermolysis Bullosa.","date":"1997","source":"Molecular medicine (Cambridge, Mass.)","url":"https://pubmed.ncbi.nlm.nih.gov/9085255","citation_count":25,"is_preprint":false},{"pmid":"10964684","id":"PMC_10964684","title":"Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas.","date":"2000","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/10964684","citation_count":24,"is_preprint":false},{"pmid":"32554866","id":"PMC_32554866","title":"Silencing of hsa_circ_0101145 reverses the epithelial-mesenchymal transition in hepatocellular carcinoma via regulation of the miR-548c-3p/LAMC2 axis.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/32554866","citation_count":24,"is_preprint":false},{"pmid":"36612197","id":"PMC_36612197","title":"S100A10 Promotes Pancreatic Ductal Adenocarcinoma Cells Proliferation, Migration and Adhesion through JNK/LAMB3-LAMC2 Axis.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36612197","citation_count":20,"is_preprint":false},{"pmid":"21573221","id":"PMC_21573221","title":"A frameshift mutation within LAMC2 is responsible for Herlitz type junctional epidermolysis bullosa (HJEB) in black headed mutton sheep.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21573221","citation_count":18,"is_preprint":false},{"pmid":"34689384","id":"PMC_34689384","title":"Novel LAMC2 fusion protein has tumor-promoting properties in ovarian carcinoma.","date":"2021","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/34689384","citation_count":17,"is_preprint":false},{"pmid":"38703300","id":"PMC_38703300","title":"LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway.","date":"2024","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38703300","citation_count":16,"is_preprint":false},{"pmid":"36412218","id":"PMC_36412218","title":"Overexpressed LAMC2 promotes trophoblast over-invasion through the PI3K/Akt/MMP2/9 pathway in placenta accreta spectrum.","date":"2022","source":"The journal of obstetrics and gynaecology research","url":"https://pubmed.ncbi.nlm.nih.gov/36412218","citation_count":15,"is_preprint":false},{"pmid":"36709879","id":"PMC_36709879","title":"LncRNA T376626 is a promising serum biomarker and promotes proliferation, migration, and invasion via binding to LAMC2 in triple-negative breast cancer.","date":"2023","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/36709879","citation_count":15,"is_preprint":false},{"pmid":"33880581","id":"PMC_33880581","title":"hsa‑miR‑5580‑3p inhibits oral cancer cell viability, proliferation and migration by suppressing LAMC2.","date":"2021","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/33880581","citation_count":14,"is_preprint":false},{"pmid":"38760717","id":"PMC_38760717","title":"Extracellular matrix marker LAMC2 targets ZEB1 to promote TNBC malignancy via up-regulating CD44/STAT3 signaling pathway.","date":"2024","source":"Molecular medicine (Cambridge, Mass.)","url":"https://pubmed.ncbi.nlm.nih.gov/38760717","citation_count":13,"is_preprint":false},{"pmid":"28032728","id":"PMC_28032728","title":"Association of lnc-LAMC2-1:1 rs2147578 and CASC8 rs10505477 Polymorphisms with Risk of Childhood Acute Lymphoblastic Leukemia.","date":"2016","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/28032728","citation_count":13,"is_preprint":false},{"pmid":"37415741","id":"PMC_37415741","title":"LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral.","date":"2023","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/37415741","citation_count":12,"is_preprint":false},{"pmid":"34606473","id":"PMC_34606473","title":"RUNX2 and LAMC2: promising pancreatic cancer biomarkers identified by an integrative data mining of pancreatic adenocarcinoma tissues.","date":"2021","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/34606473","citation_count":12,"is_preprint":false},{"pmid":"39270979","id":"PMC_39270979","title":"20(S)-Ginsenoside Rh2 overcomes gemcitabine resistance in pancreatic cancer by inhibiting LAMC2-Modulated ABC transporters.","date":"2024","source":"Journal of advanced research","url":"https://pubmed.ncbi.nlm.nih.gov/39270979","citation_count":12,"is_preprint":false},{"pmid":"39778762","id":"PMC_39778762","title":"Anticancer and therapeutic efficacy of XPO1 inhibition in pancreatic ductal adenocarcinoma through DNA damage and modulation of miR-193b/KRAS/LAMC2/ERK/AKT signaling cascade.","date":"2025","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39778762","citation_count":11,"is_preprint":false},{"pmid":"38475740","id":"PMC_38475740","title":"Knockdown of ribosome RNA processing protein 15 suppresses migration of hepatocellular carcinoma through inhibiting PATZ1-associated LAMC2/FAK pathway.","date":"2024","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38475740","citation_count":11,"is_preprint":false},{"pmid":"37891404","id":"PMC_37891404","title":"LAMC2 mitigates ER stress by enhancing ER-mitochondria interaction via binding to MYH9 and MYH10.","date":"2023","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/37891404","citation_count":10,"is_preprint":false},{"pmid":"37542131","id":"PMC_37542131","title":"LAMC2 promotes EGFR cell membrane localization and acts as a novel biomarker for tyrosine kinase inhibitors (TKIs) sensitivity in lung cancer.","date":"2023","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/37542131","citation_count":10,"is_preprint":false},{"pmid":"25888738","id":"PMC_25888738","title":"Epidermolysis bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene.","date":"2015","source":"BMC veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/25888738","citation_count":10,"is_preprint":false},{"pmid":"34533031","id":"PMC_34533031","title":"LAMC2 acts as a novel therapeutic target of cetuximab in laryngeal cancer.","date":"2021","source":"Neoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/34533031","citation_count":8,"is_preprint":false},{"pmid":"33995623","id":"PMC_33995623","title":"Intrahepatic Cholangiocarcinoma Cells Promote Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Cells by Secreting LAMC2.","date":"2021","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/33995623","citation_count":8,"is_preprint":false},{"pmid":"30285664","id":"PMC_30285664","title":"The rs2147578 C > G polymorphism in the Inc-LAMC2-1:1 gene is associated with increased neuroblastoma risk in the Henan children.","date":"2018","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30285664","citation_count":8,"is_preprint":false},{"pmid":"39595099","id":"PMC_39595099","title":"NSUN2 Promotes Head and Neck Squamous Cell Carcinoma Progression by Targeting EMT-Related Gene LAMC2 in an m5C-YBX1-Dependent Manner.","date":"2024","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/39595099","citation_count":7,"is_preprint":false},{"pmid":"29687150","id":"PMC_29687150","title":"Whole-Genome Analysis of an Extensively Drug-Resistance Empedobacter falsenii Strain Reveals Distinct Features and the Presence of a Novel Metallo-ß-Lactamase (EBR-2).","date":"2018","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29687150","citation_count":7,"is_preprint":false},{"pmid":"36582685","id":"PMC_36582685","title":"A novel lnc-LAMC2-1:1 SNP promotes colon adenocarcinoma progression by targeting miR-216a-3p/HMGB3.","date":"2022","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/36582685","citation_count":6,"is_preprint":false},{"pmid":"31390898","id":"PMC_31390898","title":"Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway.","date":"2019","source":"Experimental biology and medicine (Maywood, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/31390898","citation_count":6,"is_preprint":false},{"pmid":"10660342","id":"PMC_10660342","title":"Laminin 5 genes and Herlitz junctional epidermolysis bullosa: novel mutations and polymorphisms in the LAMB3 and LAMC2 genes. Mutations in brief no. 190. Online.","date":"1998","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/10660342","citation_count":6,"is_preprint":false},{"pmid":"35291611","id":"PMC_35291611","title":"Two Novel Mutations in LAMC2 Gene in Iranian Families Affected by Junctional Epidermolysis Bullosa.","date":"2022","source":"Reports of biochemistry & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/35291611","citation_count":4,"is_preprint":false},{"pmid":"37183943","id":"PMC_37183943","title":"Silencing of LAMC2 Reverses Epithelial Mesenchymal Transition and Inhibits Progression in Pancreatic Ductal Adenocarcinoma via Inactivation of the NF-κB Signaling Pathway.","date":"2023","source":"Critical reviews in eukaryotic gene expression","url":"https://pubmed.ncbi.nlm.nih.gov/37183943","citation_count":4,"is_preprint":false},{"pmid":"40004224","id":"PMC_40004224","title":"miR-212-5p Regulates PM2.5-Induced Apoptosis by Targeting LAMC2 and LAMA3.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40004224","citation_count":4,"is_preprint":false},{"pmid":"31898842","id":"PMC_31898842","title":"A single-nucleotide polymorphism in lnc-LAMC2-1:1 interferes with its interaction with miR-128 to alter the expression of deleted in colorectal cancer and its effect on the survival rate of subjects with ovarian cancer.","date":"2020","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31898842","citation_count":4,"is_preprint":false},{"pmid":"35432467","id":"PMC_35432467","title":"Epidermolysis Bullosa With Congenital Absence of Skin: Congenital Corneal Cloudiness and Esophagogastric Obstruction Including Extended Genotypic Spectrum of PLEC, LAMC2, ITGB4 and COL7A1.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35432467","citation_count":4,"is_preprint":false},{"pmid":"11804339","id":"PMC_11804339","title":"Alternative transcriptional initiation and splicing of mouse Lamc2 message.","date":"2001","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/11804339","citation_count":4,"is_preprint":false},{"pmid":"35669642","id":"PMC_35669642","title":"Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway.","date":"2022","source":"Computational intelligence and neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/35669642","citation_count":3,"is_preprint":false},{"pmid":"24533970","id":"PMC_24533970","title":"Novel compound heterozygous mutation in LAMC2 genes (c.79G>A and 382insT) in Herlitz junctional epidermolysis bullosa.","date":"2014","source":"The Journal of dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/24533970","citation_count":3,"is_preprint":false},{"pmid":"40680053","id":"PMC_40680053","title":"Odontogenesis-associated phosphoprotein (ODAPH) Promotes Ameloblast adhesion and alkaline phosphatase (ALP) expression via LAMC2/ ITGB6/TGF-β1 signaling pathway.","date":"2025","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/40680053","citation_count":2,"is_preprint":false},{"pmid":"41298762","id":"PMC_41298762","title":"Single-cell and bulk transcriptomics reveal Fusobacterium nucleatum promotes colorectal cancer metastasis by upregulating LAMC2 in in vitro and in vivo models.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41298762","citation_count":1,"is_preprint":false},{"pmid":"40986946","id":"PMC_40986946","title":"The multidimensional role of laminin γ2 (LAMC2) on cancer progression.","date":"2025","source":"Cancer genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40986946","citation_count":1,"is_preprint":false},{"pmid":"37829868","id":"PMC_37829868","title":"Retracted: Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway.","date":"2023","source":"Computational intelligence and neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/37829868","citation_count":1,"is_preprint":false},{"pmid":"40831397","id":"PMC_40831397","title":"Targeting FOXE1-Mediated LAMC2 Expression to Improve Preoperative Chemoradiotherapy Outcomes in Lung Cancer Patients at Risk of Brain Metastasis.","date":"2025","source":"Cancer biotherapy & radiopharmaceuticals","url":"https://pubmed.ncbi.nlm.nih.gov/40831397","citation_count":1,"is_preprint":false},{"pmid":"41392239","id":"PMC_41392239","title":"LAMC2 promotes gallbladder carcinoma metastasis through the TGF-β pathway.","date":"2025","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/41392239","citation_count":0,"is_preprint":false},{"pmid":"38648026","id":"PMC_38648026","title":"Junctional Epidermolysis Bullosa Linked to Homozygous Mutation in LAMC2 Gene: A Case Report With Eosinophil-Rich Inflammatory Infiltrate.","date":"2024","source":"The American Journal of dermatopathology","url":"https://pubmed.ncbi.nlm.nih.gov/38648026","citation_count":0,"is_preprint":false},{"pmid":"41952674","id":"PMC_41952674","title":"Acidic microenvironment-induced LAMC2 expression promotes proliferation, migration, and pathway regulation in non-small cell lung cancer cells.","date":"2026","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41952674","citation_count":0,"is_preprint":false},{"pmid":"42212402","id":"PMC_42212402","title":"Laminin Gamma 2 (LAMC2)-Targeting F(ab')2 for 89Zr Immuno-PET Imaging of Human NSCLC Xenograft Models.","date":"2026","source":"Molecular pharmaceutics","url":"https://pubmed.ncbi.nlm.nih.gov/42212402","citation_count":0,"is_preprint":false},{"pmid":"21198797","id":"PMC_21198797","title":"A Japanese-specific recurrent mutation and a novel splice site mutation in the LAMC2 gene identified in two Japanese families with Herlitz junctional epidermolysis bullosa.","date":"2010","source":"Clinical and experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/21198797","citation_count":0,"is_preprint":false},{"pmid":"41924248","id":"PMC_41924248","title":"LAMC2 Drives Airway Remodeling in COPD via EMT Regulation Through the AKT Pathway.","date":"2026","source":"International journal of chronic obstructive pulmonary disease","url":"https://pubmed.ncbi.nlm.nih.gov/41924248","citation_count":0,"is_preprint":false},{"pmid":"42203263","id":"PMC_42203263","title":"Gasdermin D antagonizes immunosuppression in prostate cancer by inducing LAMC2 degradation to block M2 macrophage polarization.","date":"2026","source":"Journal for immunotherapy of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/42203263","citation_count":0,"is_preprint":false},{"pmid":"42037995","id":"PMC_42037995","title":"Molecular mechanism of Danshen injection in treating endometrial fibrosis induced by intrauterine adhesions via the LAMC2-CD44-TGF-β1-SMAD2/3 signaling pathway.","date":"2026","source":"Frontiers in physiology","url":"https://pubmed.ncbi.nlm.nih.gov/42037995","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.14.688421","title":"Batch-Harmonized Machine Learning Framework for Cross-Cohort RNA Biomarker Discovery in Pancreatic Adenocarcinoma","date":"2025-11-14","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.14.688421","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":45010,"output_tokens":7004,"usd":0.120045,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":16160,"output_tokens":3900,"usd":0.08915,"stage2_stop_reason":"end_turn"},"total_usd":0.209195,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"Loss-of-function mutations (premature stop codons) in LAMC2, encoding the γ2 subunit of laminin-5 (nicein/kalinin), cause Herlitz junctional epidermolysis bullosa, establishing that LAMC2 is required for structural integrity of the cutaneous basement membrane zone.\",\n      \"method\": \"Genetic linkage analysis, microsatellite mapping, mutation identification by sequencing in H-JEB kindreds\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independently replicated in two simultaneous papers (PMID 8012394 and 8012393), with multiple kindreds and mutation types confirming causal loss-of-function\",\n      \"pmids\": [\"8012394\", \"8012393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"The LAMC2 gene contains 23 exons spanning 55 kb, and alternative splicing at the last exon produces two transcripts: the longer γ2 chain (exon 23) expressed broadly in epithelial tissues, and a shorter γ2* chain (using part of intron 22) expressed specifically in cerebral cortex, lung, and kidney distal tubules.\",\n      \"method\": \"Genomic library cloning, exon mapping, Northern hybridization of human embryonic tissues, cDNA analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genomic and expression analysis with tissue-specific validation, single lab\",\n      \"pmids\": [\"8786121\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"TGF-β differentially enhances LAMC2, LAMA3, and LAMB3 gene expression in epidermal keratinocytes (greater effect on LAMA3 and LAMC2 than LAMB3); TNF-α alone does not alter LAMB3 or LAMC2 expression, indicating non-coordinate cytokine regulation of laminin-5 subunit genes.\",\n      \"method\": \"Northern hybridization with specific cDNA probes in primary keratinocytes and keratinocyte cell lines treated with TGF-β and TNF-α\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cytokine treatment with Northern blot in multiple cell types, single lab\",\n      \"pmids\": [\"7635220\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Intact laminin-5 promotes cell adhesion but recombinant γ2 chain alone does not, indicating the γ2 chain lacks an autonomous cell-binding site. However, antibodies against the short arm of the γ2 chain inhibited carcinoma cell migration in vitro, implicating the γ2 chain in cell locomotion. A cis-acting element between −613 and +55 of the LAMC2 promoter drives expression specifically in migratory epithelial cells of healing wounds in transgenic mice.\",\n      \"method\": \"Cell adhesion assay with purified laminin-5 and recombinant γ2, antibody blocking migration assay, promoter-lacZ reporter transgenic mice\",\n      \"journal\": \"Matrix biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro reconstitution with antibody blocking, validated in transgenic reporter mice in vivo, multiple orthogonal methods in one study\",\n      \"pmids\": [\"10372560\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Integrity of the γ2 chain C-terminal amino acid sequences (domains I and II) is required for laminin-5 assembly: a truncating mutation in the terminal exon (γ2t) abolished laminin-5 assembly and deposition, whereas an in-frame deletion in domain V (γ2Δ4) still allowed assembly, secretion, and extracellular processing of laminin-5. This correlates a specific domain function with a mild versus severe JEB phenotype.\",\n      \"method\": \"Transfection of mutant γ2 cDNAs into γ2-null keratinocytes, immunofluorescence detection of laminin-5 deposition, patient mutation characterization\",\n      \"journal\": \"The Journal of investigative dermatology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstitution in null cells with domain-specific mutants establishing structure-function relationships, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"11564184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"TGF-β1 and HGF synergistically activate the LAMC2 promoter and induce laminin γ2 chain accumulation in colon carcinoma cells; this synergy requires the 5′ AP-1 element and an additional upstream element responsive to Smad3. The synergistic activation is specific to LAMC2 (not LAMA3 or LAMB3), explaining why γ2 chain accumulates at the invasive front of colon carcinomas.\",\n      \"method\": \"Promoter-reporter assays, Smad3 co-expression, cytokine treatment of colon carcinoma cell lines\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter dissection with defined elements and transcription factor identification, single lab\",\n      \"pmids\": [\"12519076\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"LAMC2 physically binds to EGFR in anaplastic thyroid carcinoma cells (shown by immunoprecipitation); silencing LAMC2 partially blocks EGF-mediated EGFR activation and downstream signaling, and EGFR blocking (cetuximab or siRNA) additively enhances antiproliferative effects of LAMC2 knockdown.\",\n      \"method\": \"shRNA knockdown, immunoprecipitation, Western blot for EGFR pathway activation, xenograft mouse model, rescue overexpression experiments\",\n      \"journal\": \"The Journal of clinical endocrinology and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional epistasis in vitro and in vivo, single lab\",\n      \"pmids\": [\"24170107\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"LAMC2 promotes lung adenocarcinoma migration and invasion via EMT in an integrin β1- and ZEB1-dependent manner; LAMC2 knockdown decreases traction force, migration, and invasion with reduction of EMT markers, and attenuates metastasis in mice.\",\n      \"method\": \"Genome-wide transcriptional analysis, shRNA knockdown, traction force microscopy, in vitro migration/invasion assays, mouse metastasis model\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional KD with defined pathway placement (integrin β1/ZEB1), in vivo validation, single lab\",\n      \"pmids\": [\"25591736\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"LAMB3 and LAMC2 are upregulated in gastric cancer via promoter demethylation; DNA hypomethylation correlates with gene expression, and methylation inhibitor treatment induces their expression. ChIP demonstrates enrichment of the activation histone mark H3K4me3 at both gene promoters in expressing cells.\",\n      \"method\": \"DNA methylation analysis, gene expression profiling, methylation inhibitor treatment, chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epigenetic mechanism established by ChIP and inhibitor treatment, single lab\",\n      \"pmids\": [\"21345334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Overexpression of LAMC2 (a target of miR-622) in gastric cancer cells activates the EGFR/ERK1/2-MMP7 signaling pathway, promoting cell invasion; this is shown by upregulation of phospho-EGFR, phospho-ERK1/2, and MMP7 upon LAMC2 overexpression and knockdown of CD82.\",\n      \"method\": \"LAMC2 overexpression and knockdown, Western blot for signaling proteins, cell invasion assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined pathway activation with gain/loss of function, single lab\",\n      \"pmids\": [\"28252644\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Silencing LAMC2 in cholangiocarcinoma cells suppresses EGFR signaling pathway activity, inhibiting EMT and cell invasion/migration in vitro and reducing angiogenesis (microvessel density) in vivo. The interaction between LAMC2 and EGFR signaling was confirmed: LAMC2 overexpression activates the EGFR pathway and EMT, whereas EGFR pathway inhibition phenocopies LAMC2 silencing.\",\n      \"method\": \"LAMC2 siRNA knockdown and overexpression, EGFR inhibitor treatment, EMT marker analysis, xenograft angiogenesis assay\",\n      \"journal\": \"The American journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal gain/loss of function with pathway inhibition epistasis, in vivo validation, single lab\",\n      \"pmids\": [\"31345467\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"LAMC2 promotes pancreatic cancer cell migration and invasion by phosphorylating AKT-Ser473, which enhances expression, activity, and cell-membrane accumulation of NHE1 (sodium/hydrogen exchanger 1), generating extracellular acidification; this promotes actin-dependent pseudopodial formation and EMT.\",\n      \"method\": \"LAMC2 knockdown/overexpression, Western blot for AKT phosphorylation and NHE1, extracellular pH measurement, confocal microscopy of actin/NHE1 localization\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined AKT-NHE1 signaling axis with functional readouts, single lab, multiple methods\",\n      \"pmids\": [\"32246993\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"LAMC2-null intrahepatic cholangiocarcinoma cells fail to induce EMT, migration, and invasion in hepatocellular carcinoma cells (conditioned medium experiments), demonstrating that secreted LAMC2 from cholangiocarcinoma cells acts in a paracrine manner to promote EMT of neighboring hepatocellular carcinoma cells.\",\n      \"method\": \"LAMC2 knockout (established LAMC2-KO cells), conditioned medium transfer, EMT marker analysis, migration/invasion assays\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO rescue experiment demonstrating paracrine mechanism, single lab\",\n      \"pmids\": [\"33995623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A chromosomal translocation between LAMC2 (chr1) and NR6A1 (chr9) in ovarian cancer SKOV3 cells generates a novel fusion protein (Lm-γ2F) lacking domains I and II but retaining the EGF-like domain III (DIII). This truncated form is secreted and acts as an EGFR ligand activating EGFR/AKT pathways more effectively than full-length Lm-γ2, promoting proliferation, survival, and motility of ovarian cancer cells.\",\n      \"method\": \"In situ hybridization, RT-PCR of fusion transcripts, overexpression and suppression of fusion transcripts, Western blot for EGFR/AKT signaling, mouse xenograft tumor growth assays\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — novel mechanism with gain/loss of function, in vivo validation, single lab\",\n      \"pmids\": [\"34689384\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"LAMC2 is localized in the endoplasmic reticulum (ER) of lung, breast, and liver cancer cells. Under ER stress, LAMC2 forms protein complexes with MYH9 and MYH10 to promote mitochondrial aggregation and enhanced ER-mitochondria interaction at the perinuclear region, attenuating ER stress, elevating mitochondrial membrane potential, and reducing ROS and apoptosis.\",\n      \"method\": \"Subcellular fractionation, co-immunoprecipitation of LAMC2 with MYH9/MYH10, tunicamycin-induced ER stress, mitochondrial membrane potential assays, ROS measurement, in vivo xenograft\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP defining protein complex, localization experiments with functional consequence, in vivo validation, single lab\",\n      \"pmids\": [\"37891404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"LAMC2 co-localizes with EGFR at the ER membrane; both the EGF-Lam and LamB domains of LAMC2 are required for EGFR binding. LAMC2 overexpression enhances EGFR membrane deposition and promotes EGFR transport from the ER, and LAMC2 prevents EGFR protein degradation via ubiquitination, thereby stabilizing EGFR expression.\",\n      \"method\": \"Deletion mutagenesis of LAMC2 domains, co-localization confocal imaging, EGFR membrane fractionation, ubiquitination assays, in vivo tumor growth\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion mutagenesis with functional readouts, multiple methods, single lab\",\n      \"pmids\": [\"37542131\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"LAMC2 inhibition in pancreatic cancer impairs cell cycle and induces apoptosis; LAMC2 regulates a FOSL1-AXL axis via AKT phosphorylation, and genetic LAMC2 or pharmacological AXL inhibition shows synergistic antiproliferative effect with MEK1/2 inhibitors in 2D, 3D, and patient-derived organoid PDAC models.\",\n      \"method\": \"shRNA knockdown, RNA-sequencing, AKT phosphorylation assays, AXL inhibition, combination drug assays in 2D/3D/organoids and xenograft/allograft in vivo models\",\n      \"journal\": \"Clinical cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transcriptional network defined by RNA-seq with functional validation across multiple model systems, single lab\",\n      \"pmids\": [\"36607777\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The transcription factor PATZ1, regulated downstream of RRP15, directly controls LAMC2 (and LAMB3) expression; loss of RRP15 reduces PATZ1 protein, decreasing LAMC2/LAMB3, which in turn suppresses the integrin β4 (ITGB4)/FAK/NF-κB signaling pathway and inhibits HCC cell migration.\",\n      \"method\": \"RRP15 knockdown, Western blot for PATZ1 and LAMC2, cell migration/invasion assays, in vivo mouse model\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined upstream regulator-transcription factor-LAMC2 axis with in vivo validation, single lab\",\n      \"pmids\": [\"38475740\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LAMC2 expression is induced by canonical TGF-β/SMAD2 signaling; in turn, LAMC2 feeds back to enhance TGF-β signaling by binding to TGF-β receptor II (TGF-βRII), forming a positive feedback loop that promotes gallbladder carcinoma EMT and metastasis.\",\n      \"method\": \"Western blot, RT-qPCR, TGF-β/SMAD2 pathway inhibition, LAMC2 silencing, in vivo metastasis model, organoid assays\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — bidirectional pathway relationship established with gain/loss of function and in vivo validation, single lab\",\n      \"pmids\": [\"41392239\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NSUN2, an m5C methyltransferase, promotes LAMC2 mRNA stability through m5C modification in an YBX1-dependent manner; NSUN2 knockdown reduces m5C modification at LAMC2 and decreases LAMC2 expression, suppressing EMT and tumor progression in head and neck squamous cell carcinoma.\",\n      \"method\": \"m5C-Bis-Seq (transcriptome-wide m5C profiling), NSUN2 knockdown, in vitro and in vivo functional assays\",\n      \"journal\": \"Biomedicines\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transcriptome-wide m5C mapping identifies LAMC2 as target, single lab\",\n      \"pmids\": [\"39595099\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Hypoxia induces global histone lactylation and specifically increases H3K9 lactylation (H3K9la) at the LAMC2 promoter, enhancing LAMC2 transcription and promoting ESCC invasion.\",\n      \"method\": \"Quantitative proteomics of histone modifications, MNase ChIP-seq for H3K9la, RNA-seq, in vitro and in vivo ESCC models\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq demonstrates H3K9la enrichment at LAMC2 promoter with functional consequence, single lab\",\n      \"pmids\": [\"38989468\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LAMC2 promotes trophoblast invasion via the PI3K/Akt/MMP2/MMP9 signaling pathway: LAMC2 overexpression elevates phospho-Akt, MMP2, and MMP9 protein levels and increases invasion/migration; PI3K inhibitor LY294002 abolishes these effects.\",\n      \"method\": \"LAMC2 overexpression/knockdown in HTR8/SVneo cells, Western blot for PI3K/Akt/MMP2/9, invasion/migration assays, PI3K inhibitor treatment\",\n      \"journal\": \"The journal of obstetrics and gynaecology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pathway inhibitor epistasis with gain/loss of function, single lab\",\n      \"pmids\": [\"36412218\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LAMC2 promotes TNBC proliferation and migration by upregulating CD44 and activating STAT3 signaling; luciferase reporter assays showed LAMC2 targets the ZEB1 promoter to drive its transcription.\",\n      \"method\": \"Luciferase reporter assay (ZEB1 promoter), Western blot for CD44/STAT3, cell viability and migration assays, xenograft mouse model\",\n      \"journal\": \"Molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase assay defining transcriptional target with in vivo validation, single lab\",\n      \"pmids\": [\"38760717\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GSDMD binds LAMC2 directly and induces its ubiquitin-mediated proteasomal degradation; GSDMD deficiency stabilizes LAMC2, driving M2 macrophage polarization and CXCL5 secretion, which activates the AKT/NF-κB axis and suppresses cytotoxic T lymphocyte activity in prostate cancer.\",\n      \"method\": \"GSDMD deletion models, protein interaction analysis (co-IP), ubiquitination assays, immune cell profiling, correlative analysis in human PCa samples\",\n      \"journal\": \"Journal for immunotherapy of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — protein interaction and ubiquitination mechanism identified with in vivo immune profiling, single lab\",\n      \"pmids\": [\"42203263\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ODAPH physically interacts with LAMC2 (confirmed by co-immunoprecipitation) and activates the LAMC2/ITGB6/TGF-β1/ALP signaling axis to promote ameloblast adhesion and mineralization; integrin inhibition (CWHM-12) abrogates ODAPH-mediated TGF-β1/ALP induction.\",\n      \"method\": \"Co-immunoprecipitation, ODAPH overexpression, integrin inhibitor treatment, Western blot for pathway proteins, ALP activity assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP confirming interaction, inhibitor epistasis defining signaling axis, single lab\",\n      \"pmids\": [\"40680053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"LAMC2 promotes gemcitabine resistance in pancreatic cancer via upregulation of ATP-binding cassette (ABC) transporters and regulation of EMT; LAMC2 knockdown enhances gemcitabine sensitivity and apoptosis in PC cell lines.\",\n      \"method\": \"siRNA knockdown, cell viability and apoptosis assays, gene expression correlation of ABC transporters\",\n      \"journal\": \"Carcinogenesis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional KD with defined molecular correlate (ABC transporters) but mechanistic link is correlational, single lab\",\n      \"pmids\": [\"33624791\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"miR-146a directly targets LAMC2 (validated by dual-luciferase reporter assay) to suppress the PI3K/Akt signaling pathway, increasing chemosensitivity of ovarian cancer cells to docetaxel/taxane; hUCMSC-derived exosomes delivering miR-146a reduce OC cell growth and resistance via this LAMC2-PI3K/Akt axis.\",\n      \"method\": \"StarBase/miRSearch database prediction, dual-luciferase reporter assay, miR-146a inhibitor transfection, LAMC2 overexpression, PI3K/Akt Western blot\",\n      \"journal\": \"International journal of molecular medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — luciferase validation of miR target site plus pathway assays, single lab, no direct LAMC2 domain or protein mechanism\",\n      \"pmids\": [\"32626953\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Mouse Lamc2 generates a smaller mRNA isoform via an alternative transcriptional start site within exon 19 (with promoter activity confirmed by reporter assay) and an alternatively spliced exon 19B containing stop codons, revealing distinct mechanisms of alternative mRNA generation between mouse and human LAMC2.\",\n      \"method\": \"5′ RACE, primer extension, genomic DNA analysis, alkaline phosphatase reporter assay\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, promoter reporter assay plus RACE, no functional consequence of isoform defined\",\n      \"pmids\": [\"11804339\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LAMC2 encodes the γ2 chain of laminin-5 (laminin-332), which is essential for basement membrane structural integrity (loss-of-function mutations cause junctional epidermolysis bullosa); the γ2 chain's C-terminal domains are required for laminin-5 heterotrimer assembly and secretion, while its EGF-like domain III can act as an EGFR ligand. In cancer cells, LAMC2 localizes at the ER where it binds EGFR to promote its membrane transport and prevent ubiquitin-mediated degradation; LAMC2 also forms complexes with MYH9/MYH10 at ER-mitochondria contact sites to attenuate ER stress. Extracellularly, LAMC2 drives EMT, migration, and invasion through multiple downstream pathways including integrin β1/ZEB1, EGFR/ERK/MMP7, AKT/NHE1-mediated extracellular acidification, PI3K/AKT/MMP2/9, FOSL1-AXL/AKT, and CD44/STAT3/ZEB1; its transcription is induced by TGF-β/SMAD2/AP-1 and HGF synergy via defined promoter elements, and epigenetically regulated by promoter demethylation, H3K9 lactylation under hypoxia, and NSUN2-mediated m5C mRNA stabilization. GSDMD antagonizes LAMC2 function by inducing its ubiquitin-mediated proteasomal degradation, preventing M2 macrophage polarization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LAMC2 encodes the γ2 chain of laminin-5 (laminin-332), a basement membrane glycoprotein whose loss-of-function mutations cause Herlitz junctional epidermolysis bullosa, establishing its essential role in cutaneous basement membrane integrity [#0]. Assembly of the laminin-5 heterotrimer requires the integrity of the γ2 C-terminal domains (I and II); a terminal-exon truncation abolishes assembly and deposition, whereas a domain V in-frame deletion permits secretion and processing, correlating domain function with disease severity [#4]. The isolated γ2 chain lacks an autonomous cell-binding site, yet antibodies against its short arm block carcinoma cell migration, and a defined promoter element drives expression in migratory epithelial cells of healing wounds [#3]. Beyond its structural role, LAMC2 acts as a potent driver of epithelial-mesenchymal transition, migration, and invasion across many carcinomas, signaling through integrin β1/ZEB1 [#7], EGFR/ERK/MMP7 [#9], AKT-driven NHE1 extracellular acidification [#11], PI3K/AKT/MMP2/9 [#21], FOSL1-AXL/AKT [#16], and CD44/STAT3/ZEB1 with direct transcriptional activation of ZEB1 [#22], and it can act in a paracrine manner via secretion [#12]. A central function is regulation of EGFR: LAMC2 localizes to the endoplasmic reticulum where it binds EGFR via its EGF-Lam and LamB domains, promoting EGFR membrane transport and preventing its ubiquitin-mediated degradation [#15], and a LAMC2-NR6A1 fusion retaining the EGF-like domain III acts as a secreted EGFR ligand [#13]. At the ER, LAMC2 also complexes with MYH9/MYH10 to enhance ER-mitochondria contact and attenuate ER stress and apoptosis [#14]. Its transcription is induced by TGF-β/SMAD signaling—including a TGF-βRII positive-feedback loop [#18]—synergizing with HGF via AP-1 and Smad-responsive promoter elements [#5], and is epigenetically controlled by promoter demethylation [#8], hypoxia-driven H3K9 lactylation [#20], and NSUN2/YBX1-mediated m5C mRNA stabilization [#19]. GSDMD antagonizes LAMC2 by inducing its ubiquitin-mediated proteasomal degradation, linking LAMC2 to M2 macrophage polarization and immune suppression [#23].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Established that LAMC2 is genetically required for basement membrane integrity by linking loss-of-function mutations to a heritable blistering disease.\",\n      \"evidence\": \"Genetic linkage and mutation sequencing in Herlitz junctional epidermolysis bullosa kindreds\",\n      \"pmids\": [\"8012394\", \"8012393\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define which γ2 domains mediate assembly versus secretion\", \"No molecular mechanism for how γ2 loss destabilizes the basement membrane\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Defined the LAMC2 gene structure and revealed tissue-specific alternative splicing generating a distinct γ2* transcript, raising the possibility of isoform-specific functions.\",\n      \"evidence\": \"Genomic cloning, exon mapping, and Northern hybridization of human embryonic tissues\",\n      \"pmids\": [\"8786121\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional role assigned to the γ2* isoform\", \"Protein-level confirmation of the short isoform absent\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Distinguished the γ2 chain's structural adhesion role from a migration-promoting role, showing it lacks an autonomous cell-binding site yet contributes to locomotion.\",\n      \"evidence\": \"Cell adhesion assays with recombinant γ2, antibody-blocking migration assays, and promoter-lacZ transgenic mice\",\n      \"pmids\": [\"10372560\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular partner mediating migration not identified\", \"Promoter element drivers (transcription factors) not yet defined\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Mapped the γ2 C-terminal domains as the determinant of laminin-5 assembly, providing a structure-function basis for mild versus severe disease.\",\n      \"evidence\": \"Transfection of domain-specific mutant γ2 cDNAs into γ2-null keratinocytes with immunofluorescence of laminin-5 deposition\",\n      \"pmids\": [\"11564184\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic structural model of the assembly interface lacking\", \"How partial assembly translates to residual basement membrane function unresolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Identified the transcriptional logic for LAMC2 overexpression at the invasive tumor front, showing TGF-β/HGF synergy acts specifically on the LAMC2 promoter.\",\n      \"evidence\": \"Promoter-reporter assays with Smad3 co-expression and cytokine treatment in colon carcinoma cells\",\n      \"pmids\": [\"12519076\", \"7635220\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not establish the downstream invasive effectors\", \"Specificity for LAMC2 over LAMA3/LAMB3 mechanism incompletely explained\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected LAMC2 to oncogenic EGFR signaling, demonstrating physical binding to EGFR and pathway dependence in carcinoma.\",\n      \"evidence\": \"Co-immunoprecipitation, shRNA knockdown, EGFR pathway Western blots, and xenografts in thyroid and gastric cancer cells\",\n      \"pmids\": [\"24170107\", \"28252644\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding interface and subcellular site of LAMC2-EGFR interaction not yet defined\", \"Single Co-IP without reciprocal structural validation\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolved multiple downstream invasion axes (integrin β1/ZEB1, AKT/NHE1 acidification, PI3K/AKT/MMP, FOSL1-AXL) and showed paracrine secreted LAMC2 drives EMT in neighboring cells.\",\n      \"evidence\": \"Knockdown/overexpression, traction force microscopy, extracellular pH measurement, conditioned-medium transfer, and metastasis models across lung, pancreatic, and cholangiocarcinoma\",\n      \"pmids\": [\"25591736\", \"32246993\", \"33995623\", \"36607777\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Receptors mediating paracrine LAMC2 signaling not all identified\", \"Relative contribution of each axis in vivo unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Reassigned a major LAMC2 function to intracellular ER compartments, where it stabilizes EGFR against degradation and engages MYH9/MYH10 to attenuate ER stress.\",\n      \"evidence\": \"Domain-deletion mutagenesis, subcellular fractionation, co-IP, ubiquitination assays, and mitochondrial/ROS readouts in lung, breast, and liver cancer cells\",\n      \"pmids\": [\"37542131\", \"37891404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How a secreted basement membrane protein is retained in the ER mechanistically unresolved\", \"Identity of the EGFR E3 ligase that LAMC2 antagonizes unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established multilayered upstream control of LAMC2, spanning a TGF-β receptor feedback loop, RRP15-PATZ1 transcription, hypoxic histone lactylation, and m5C mRNA stabilization.\",\n      \"evidence\": \"Pathway inhibition, ChIP-seq for H3K9la, m5C-Bis-Seq, luciferase reporters, and in vivo models across gallbladder, HCC, ESCC, HNSCC, and TNBC\",\n      \"pmids\": [\"41392239\", \"38475740\", \"38989468\", \"39595099\", \"38760717\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Hierarchy and crosstalk among these regulatory inputs not integrated\", \"Cell-type specificity of each regulatory layer untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked LAMC2 stability to immune evasion and to non-malignant adhesion/mineralization, showing GSDMD-driven degradation regulates macrophage polarization and an ODAPH-LAMC2-integrin axis governs ameloblast function.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, and immune profiling in prostate cancer; co-IP and integrin inhibition in ameloblasts\",\n      \"pmids\": [\"42203263\", \"40680053\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"GSDMD-LAMC2 binding interface not mapped\", \"Whether ER-resident versus secreted LAMC2 pools are differentially degraded unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How LAMC2 partitions between its canonical secreted basement-membrane role and its non-canonical intracellular ER/EGFR-stabilizing role, and what governs this switch, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of LAMC2 in ER complexes\", \"Mechanism retaining LAMC2 in the ER versus secreting it is undefined\", \"Causal ordering between transcriptional, epigenetic, and post-translational controls not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [15, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [14, 15]},\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [12, 13]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"laminin-5 (laminin-332)\"],\n    \"partners\": [\"EGFR\", \"MYH9\", \"MYH10\", \"TGFBR2\", \"GSDMD\", \"ODAPH\", \"ITGB1\", \"ITGB4\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}