Affinage

LAMB3

Laminin subunit beta-3 · UniProt Q13751

Length
1172 aa
Mass
129.6 kDa
Annotated
2026-06-10
92 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LAMB3 encodes the β3 chain of laminin 5/332, a basement-membrane component essential for dermal-epidermal adhesion and hemidesmosome assembly (PMID:7698759, PMID:9271670). The β3 chain is a limiting subunit for laminin trimer assembly: it co-assembles with endogenous α3 and γ2 chains to deposit functional laminin in basement membranes, and restoring β3 alone is sufficient to rebuild laminin-332 and rescue adhesion phenotypes (PMID:16871230, PMID:29946029). Loss-of-function mutations—nonsense, frameshift, splice-altering, and translation-reducing variants—abolish or attenuate laminin 332 and cause junctional epidermolysis bullosa, with milder hypomorphic alleles producing generalized atrophic benign EB (PMID:7698759, PMID:7706760, PMID:9501007, PMID:39357391); β3 also functionally interacts with collagen XVII at the hemidesmosome anchoring complex, as shown by digenic JEB (PMID:10577906). Within the epithelium, LAMB3 engages integrin partners (notably ITGB4/α6β4 and ITGA6) to coordinate hemidesmosome formation, keratinization, and wound repair (PMID:29946029, PMID:41960183). In cancer and fibrotic contexts, LAMB3 is markedly upregulated and signals through integrin-coupled FAK/ERK and PI3K/AKT cascades to drive proliferation, invasion, metastasis, EMT, chemoresistance, and immune suppression (PMID:30850586, PMID:40540648, PMID:38102338, PMID:42154006); it physically associates with LAMC2 and with ITGB4/MDFI to propagate these signals (PMID:36612197, PMID:38375821). Its expression is controlled at multiple levels: transcriptionally by TGF-β/Smad with promoter chromatin opening (PMID:7635220, PMID:41412528), by NF-κB(P65) (PMID:37454278), by FOXQ1 (PMID:38297082), and by the BRD2/acetylated-ELK4 complex (PMID:32398865); post-transcriptionally by NAT10-mediated ac4C mRNA stabilization (PMID:40540648) and by 3'UTR-targeting microRNAs including miR-1298 and miR-24-3p (PMID:27698189, PMID:32039003).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1994 High

    Established LAMB3 as genetically essential for laminin 5 and skin adhesion by showing that nonsense mutations eliminate the protein and cause Herlitz JEB.

    Evidence Northern, RT-PCR, and sequencing of keratinocyte mRNA from H-JEB patients

    PMID:7698759

    Open questions at the time
    • Did not define how β3 assembles with partner chains
    • No structural basis for adhesion loss
  2. 1995 High

    Defined the complete LAMB3 gene structure, providing the framework to map and interpret JEB mutations.

    Evidence Sequencing of overlapping phage clones and exon-intron boundaries

    PMID:7774918

    Open questions at the time
    • Structural map alone does not assign functional domains to phenotypes
  3. 1995 Medium

    Linked specific short-arm domain VI mutations to milder GABEB and identified TGF-β as a non-coordinate inducer of LAMB3, opening regulatory study of the gene.

    Evidence Mutation analysis with EM/immunofluorescence; Northern hybridization after cytokine treatment of keratinocytes

    PMID:7635220 PMID:7706760

    Open questions at the time
    • TGF-β transcriptional mechanism not resolved at this stage
    • Domain VI interaction with laminin 6 inferred, not biochemically shown
  4. 1996 High

    Showed recurrent CpG nonsense mutations dominate the H-JEB mutational spectrum, explaining allele recurrence across families.

    Evidence PCR, restriction digestion, and haplotype analysis across 14 families

    PMID:8824879

    Open questions at the time
    • Does not address modifiers of phenotype severity
  5. 1998 High

    Demonstrated that hypomorphic LAMB3 alleles (splice-altering missense, mRNA-destabilizing frameshift) produce reduced but partly functional laminin and milder disease, establishing a dosage/quality genotype-phenotype axis.

    Evidence RT-PCR splice analysis, mRNA decay assays, sequencing, and genotype-phenotype correlation across multiple patients

    PMID:9501007 PMID:9690563 PMID:9767254

    Open questions at the time
    • Quantitative threshold of functional laminin needed for adhesion undefined
  6. 1997 High

    Provided in vivo loss-of-function proof that LamB3 is required for hemidesmosome ultrastructure via a mouse IAP-insertion model.

    Evidence Linkage, Northern, immunohistochemistry, and EM of mutant mouse skin

    PMID:9271670

    Open questions at the time
    • Did not test which partner chain assembly step is rate-limiting
  7. 1999 High

    Revealed functional interaction between LAMB3 and COL17A1 at the anchoring filament complex through digenic JEB.

    Evidence Mutation analysis, skin immunofluorescence, and hemidesmosome EM

    PMID:10577906

    Open questions at the time
    • Direct physical β3-collagen XVII contact not demonstrated
  8. 2006 Medium

    Established β3 as the limiting subunit for laminin-5 trimer assembly by showing transgenic β3 co-assembles with endogenous α3/γ2 to rebuild basement-membrane laminin in deficient mice.

    Evidence Prenatal adenoviral/AAV LAMB3 delivery and immunohistochemical co-assembly assessment in H-JEB mice

    PMID:16871230

    Open questions at the time
    • Single study with partial rescue
    • Stoichiometry of assembly not quantified
  9. 2011 Medium

    Identified epigenetic control of LAMB3 (promoter demethylation and H3K4me3) as a mechanism of its derepression in cancer.

    Evidence Methylation/expression profiling, H3K4me3 ChIP, and methylation-inhibitor treatment in gastric cancer cells

    PMID:21345334

    Open questions at the time
    • Did not identify the transcription factors recruited to the active promoter
  10. 2013 Medium

    First established a functional pro-invasive/metastatic role for LAMB3 in cancer through loss-of-function.

    Evidence siRNA/shRNA knockdown with invasion assays and in vivo metastasis models in lung cancer

    PMID:23441154

    Open questions at the time
    • Downstream signaling not yet mapped
    • Single lab
  11. 2016 High

    Placed LAMB3 downstream of oncogenic KRAS as a synthetic-lethal node, linking it to FAK and to microRNA control.

    Evidence miR-TRAP target capture, knockdown, and rescue co-expression with in vivo tumor growth

    PMID:27698189

    Open questions at the time
    • Mechanism by which LAMB3 sustains KRAS-driven survival not fully defined
  12. 2018 High

    Demonstrated functional therapeutic restoration of laminin 332 by nonsense readthrough and by monoallelic gene correction, reconstituting adhesion and integrin polarization.

    Evidence Gentamicin readthrough across 8 PTC constructs and CRISPR/Cas9 HDR correction, with 3D skin equivalents and in vivo grafting

    PMID:29946029 PMID:30122422

    Open questions at the time
    • Durability and efficiency of correction in patient tissue not established
  13. 2018 Medium

    Connected LAMB3 to specific oncogenic signaling axes (c-MET/AKT-driven EMT) in epithelial cancer.

    Evidence siRNA knockdown with invasion assays and Western blot for EMT markers, AKT, and c-MET in thyroid cancer

    PMID:29426928

    Open questions at the time
    • Whether c-MET is a direct LAMB3 effector unresolved
  14. 2019 Medium

    Showed LAMB3 drives PDAC growth and metastasis via PI3K/AKT activation.

    Evidence siRNA knockdown, cell-cycle/apoptosis assays, xenograft and metastasis models, PI3K/AKT Western blot

    PMID:30850586

    Open questions at the time
    • Receptor coupling LAMB3 to PI3K/AKT not identified here
  15. 2020 High

    Defined direct transcriptional and post-transcriptional regulators of LAMB3 in cancer and linked it to AKT-FOXO suppression.

    Evidence ChIP/luciferase/Co-IP for BRD2-ELK4 promoter binding with JQ1; dual-luciferase 3'UTR assay for miR-24-3p with rescue

    PMID:32039003 PMID:32398865

    Open questions at the time
    • Relative contribution of each regulator in vivo not weighted
  16. 2022 Medium

    Confirmed direct LAMB3-LAMC2 physical interaction and identified additional upstream regulators (S100A10/JNK, PIGR-REST repression).

    Evidence Co-IP for LAMB3-LAMC2 and PIGR-REST, JNK inhibition, and rescue experiments in PDAC and CRC

    PMID:35992840 PMID:36612197

    Open questions at the time
    • Single-lab Co-IP without reciprocal structural validation
    • Stoichiometry of LAMB3-LAMC2 in tumor context unknown
  17. 2023 High

    Established NF-κB(P65) as a direct LAMB3 transcriptional activator and connected LAMB3 to integrin α3β1/FAK signaling in inflammation.

    Evidence Dual-luciferase, ChIP-PCR, RNA-seq, and NF-κB inhibitor treatment in intestinal inflammation

    PMID:37454278

    Open questions at the time
    • Whether the FAK output is identical across tissues not tested
  18. 2023 Medium

    Broadened LAMB3 signaling outputs to RhoA/ROCK1/MYL9 cytoskeletal remodeling, NRF2-dependent radioresistance, and integrin/FAK-driven metastasis in resistant melanoma.

    Evidence Gain/loss-of-function with pharmacological pathway manipulation in stromal cells, melanoma, and nasopharyngeal carcinoma, plus in vivo models

    PMID:36947579 PMID:37801199 PMID:38102338

    Open questions at the time
    • These context-specific axes share an upstream integrin step that is not directly compared
    • Single lab per axis
  19. 2023 Medium

    Identified a translation-level disease mechanism (uORF-creating 5'UTR variant) and a ribosome-editing therapeutic strategy for PTC alleles.

    Evidence Luciferase translation assays, minigene splicing, structural analysis, and RpL35-ligand readthrough reporter assays

    PMID:38282649 PMID:39357391

    Open questions at the time
    • Translational variant validated in reporter, not patient protein for the 5'UTR case
    • Ribosome-editing selectivity tested only in reporters
  20. 2024 High

    Resolved layered control and feedback of LAMB3 in cancer—NAT10 ac4C mRNA stabilization, FOXQ1/PARP1 transcriptional activation, YAP-TEAD4 feedback, MDFI/ITGB4 physical complex, and CRABP2 induction—each coupling LAMB3 to FAK/ERK, PI3K/AKT, MAPK, or WNT/β-catenin signaling and to immune suppression.

    Evidence acRIP, ChIP-seq/ChIP-PCR, Co-IP/MS, ubiquitination assays, RNA-seq, and in vivo tumor/immune models across PDAC, ovarian, CRC, and prostate cancer

    PMID:38297082 PMID:38375821 PMID:39016677 PMID:39038078 PMID:40540648

    Open questions at the time
    • How a secreted matrix subunit triggers PD-L1/immune programs mechanistically incomplete
    • Most axes shown in one cancer type each
  21. 2024 Medium

    Extended LAMB3 immunosuppressive and stromal functions to LAMB3-CXCL2-driven CAF infiltration and to ITGA6-coordinated epithelial repair, identifying druggable upstream regulators (melatonin, retinoic acid).

    Evidence RNA-seq, knockdown/overexpression, immune profiling, and in vivo models in TNBC and gingival/wound repair

    PMID:39306019 PMID:41960183

    Open questions at the time
    • Direct vs indirect LAMB3 control of CXCL2 not dissected
    • Single lab per system
  22. 2025 High

    Established LAMB3 as a profibrotic effector: TGF-β/Smad opens LAMB3 promoter chromatin to drive PI3K/AKT-dependent myofibroblast differentiation and renal fibrosis.

    Evidence Integrated ATAC-seq/RNA-seq, kidney-targeted LAMB3 knockdown, and Smad/AKT Western blot in a hypoxic fibrosis model

    PMID:41412528

    Open questions at the time
    • Whether fibrosis depends on secreted laminin or intracellular signaling not separated
  23. 2026 Medium

    Mapped a tumor-stroma circuit in which secreted LAMB3 drives LRRC15+ fibroblast differentiation via ITGB1/FAK/MAPK and FOSL2, suppressing T cells and limiting PD-1 blockade.

    Evidence Single-cell atlas, gain/loss-of-function, FAK inhibition, ChIP for FOSL2-LRRC15, and orthotopic immune-competent models

    PMID:42154006

    Open questions at the time
    • Receptor partner on fibroblasts not uniquely defined
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single matrix subunit switches between its structural adhesion role and a signaling/immunomodulatory role, and whether tumor effects require secreted laminin-332 assembly versus monomeric β3, remains unresolved.
  • No structural model of β3 in tumor signaling complexes
  • Direct receptor(s) coupling LAMB3 to PI3K/AKT vs FAK/ERK not unified
  • Whether trimer assembly is required for oncogenic signaling untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2
Partners
COL17A1ITGA6ITGB4LAMC2MDFI
Complex memberships
hemidesmosome anchoring filament complexlaminin 332 (laminin 5)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Homozygous nonsense mutations (premature termination codons) in LAMB3, encoding the β3 chain of laminin 5, cause complete absence of laminin 5 protein and result in Herlitz junctional epidermolysis bullosa (H-JEB), establishing LAMB3 as essential for laminin 5 assembly and dermal-epidermal adhesion. Northern hybridization, RT-PCR, direct nucleotide sequencing of keratinocyte mRNA, genomic DNA verification Genomics High 7698759
1995 The human LAMB3 gene consists of 23 exons spanning ~29 kb, encoding 1172 amino acids; its exon-intron organization is more compact than LAMB1, and this structure was used to establish the molecular basis of JEB mutations. Characterization of overlapping lambda phage DNA clones, sequencing of exon-intron boundaries, comparison with LAMB1 gene structure Genomics High 7774918
1995 Mutations in LAMB3 exons 3 and 7 (encoding part of domain VI of the β3 chain short arm) cause generalized atrophic benign epidermolysis bullosa; the domain VI globular domain is postulated to mediate interaction of laminin 5 with laminin 6 (K-laminin), and its disruption reduces epidermal-dermal adhesion. PCR amplification of genomic DNA, heteroduplex analysis, nucleotide sequencing, immunofluorescence and immunoelectron microscopy, transmission electron microscopy The Journal of investigative dermatology High 7706760
1995 TGF-β upregulates LAMB3 gene expression in human epidermal keratinocytes (as well as HaCaT and Balb/K cells), whereas TNF-α alone does not alter LAMB3 expression; the three laminin 5 subunit genes (LAMA3, LAMB3, LAMC2) are not coordinately regulated by these cytokines. Northern hybridization with specific cDNA probes, cytokine treatment of cultured keratinocytes FEBS letters Medium 7635220
1996 Two recurrent nonsense mutations in LAMB3, R42X and R635X (at CpG dinucleotides), account for over 50% of mutant LAMB3 alleles in H-JEB families; haplotype analysis demonstrated R635X arose on different genetic backgrounds, confirming CpG hypermutability as a mechanism. PCR, restriction enzyme digestion, haplotype analysis with intragenic polymorphisms, pedigree analysis Human molecular genetics High 8824879
1997 Insertion of an intracisternal-A particle (IAP) into the LamB3 coding sequence in mice abolishes LamB3 mRNA and laminin-5 protein expression, causing sub-epithelial blisters and abnormal hemidesmosomes lacking sub-basal dense plates, establishing a functional role for laminin-5/LAMB3 in hemidesmosome formation. Linkage analysis, Northern blot, immunohistochemistry, DNA sequence analysis of IAP insertion site, transmission electron microscopy Mammalian genome High 9271670
1998 A missense mutation E210K (628G→A) at the last nucleotide of LAMB3 exon 7 causes both an amino acid substitution and aberrant splicing, generating multiple aberrant mRNA species and reduced expression of laminin 5 with altered biological activity, resulting in a mild (non-lethal) JEB phenotype. RT-PCR analysis of aberrant splice variants, sequencing, mRNA decay analysis, immunofluorescence Biochemical and biophysical research communications High 9501007
1998 The LAMB3 missense mutation E210K in compound heterozygosity with a nonsense mutation is predictive of generalized atrophic benign EB phenotype; the combination of a null allele and E210K allows reduced expression of a partly functional laminin 5 protein. PCR, heteroduplex analysis, direct sequencing, genotype-phenotype correlation across three patients The British journal of dermatology Medium 9767254
1998 A LAMB3 frameshift mutation (1367delAC) causes accelerated mRNA decay, rendering the transcript undetectable by RT-PCR; a missense mutation (C293S) in the other allele results in reduced laminin 5 expression in generalized atrophic benign EB. Heteroduplex scanning, direct automated sequencing, RT-PCR for mRNA stability assessment Laboratory investigation High 9690563
1999 Digenic JEB can result from mutations in both COL17A1 and LAMB3: compound heterozygous COL17A1 null mutations combined with one LAMB3 null allele (R635X heterozygosity) causes absence of collagen XVII and attenuated laminin 5 expression, rudimentary hemidesmosome structure, and severe blistering—demonstrating functional interaction between these two hemidesmosome-anchoring filament complex proteins. Mutation analysis by sequencing, immunofluorescence of skin, electron microscopy of hemidesmosome structure American journal of human genetics High 10577906
2004 A synonymous LAMB3 variant (3009C→T in exon 20) creates a novel exonic splice site that is preferentially used by the spliceosome over the wild-type splice site despite having a lower splice score (68.6 vs. 92.2); the resulting aberrant mRNA leads to a stop codon in exon 21 and undergoes allele-specific nonsense-mediated mRNA decay. DNA sequencing, RT-PCR analysis of splice variants, computational splice-site scoring, immunohistochemistry/immunoelectron microscopy Laboratory investigation High 15311214
2006 Prenatal delivery of LAMB3 cDNA via adenoviral and AAV vectors to laminin-5 β3-deficient mice showed that the transgenic β3 chain assembles with endogenous partner chains (α3 and γ2) to produce laminin-5, which deposits in basement membranes of skin and mucosae, reducing tissue separation—demonstrating that LAMB3/β3 chain is a limiting subunit for laminin-5 trimer assembly. In vivo prenatal gene delivery, immunohistochemistry for laminin-5, co-assembly assessment in basement membranes of H-JEB mice Gene therapy Medium 16871230
2007 Multiple distinct second-site mutations in LAMB3 can correct the germline E210K mutation in vivo (revertant mosaicism), restoring laminin-332 expression in naturally corrected keratinocytes; different correcting mechanisms (splice site alterations, missense changes) all restored normal laminin-332, confirming the necessity of intact LAMB3 for laminin-332 assembly. DNA analysis of revertant keratinocytes from multiple biopsy specimens, immunofluorescence for laminin-332, sequencing of second-site mutations The Journal of clinical investigation High 17476356
2011 LAMB3 expression in gastric cancer is regulated epigenetically: promoter demethylation (DNA hypomethylation) is associated with LAMB3 upregulation, and the active histone mark H3K4me3 is associated with its expression; treatment with a methylation inhibitor induces LAMB3 expression in silenced cell lines. Combined DNA methylation and gene expression analysis, chromatin immunoprecipitation (ChIP) assay for H3K4me3, methylation inhibitor treatment Biochemical and biophysical research communications Medium 21345334
2013 Knockdown of LAMB3 suppresses invasion and metastasis of lung cancer cells in vitro and in vivo, establishing a functional role for LAMB3 in cancer cell invasive behavior. siRNA and lentiviral shRNA knockdown, invasion/migration assays in vitro, in vivo tumor metastasis models PloS one Medium 23441154
2016 miR-1298 inhibits KRAS-driven cancer cell growth by directly targeting LAMB3 (and FAK); silencing LAMB3 alone recapitulates the synthetic lethal effect of miR-1298, while co-expression of LAMB3 and FAK rescues miR-1298-induced cell death, placing LAMB3 downstream of mutant KRAS signaling. miR-TRAP affinity purification to identify LAMB3 as miR-1298 target, siRNA knockdown, rescue co-expression experiments, in vivo tumor growth assays Cancer research High 27698189
2018 Gentamicin induces readthrough of LAMB3 premature termination codons (including R635X and C290X) in H-JEB keratinocytes, producing full-length laminin β3 in a dose-dependent manner; this restored laminin 332 assembly, secretion, deposition at the dermal-epidermal junction, proper α6β4 integrin polarization, and corrected abnormal cell morphology, poor growth, poor adhesion, and hypermotility. Transfection of expression vectors with 8 different LAMB3 nonsense mutations, lentiviral stable transduction, gentamicin treatment, immunoblot, immunofluorescence, 3D skin equivalent model Proceedings of the National Academy of Sciences of the United States of America High 29946029
2018 LAMB3 suppression in papillary thyroid cancer reduces cell migration and invasion via downregulation of EMT-associated proteins (N-cadherin, vimentin, slug) and inhibition of MMP9; LAMB3 inhibition also significantly decreases AKT phosphorylation and inhibits c-MET transcription, indicating LAMB3 promotes invasion via the HGF/c-MET/AKT axis. siRNA knockdown, migration/invasion assays, Western blot for EMT markers, AKT phosphorylation, and c-MET Scientific reports Medium 29426928
2018 CRISPR/Cas9-mediated HDR using an adenovector (Cas9/gRNA targeting intron 2) and an integration-defective lentiviral vector (promoterless LAMB3 cDNA with splice acceptor) restores monoallelic LAMB3 expression in JEB keratinocytes; monoallelic correction was sufficient to restore adhesion, colony formation, and normal dermal-epidermal junction in skin equivalents transplanted onto immunodeficient mice. CRISPR/Cas9 HDR gene correction, in vitro adhesion and colony formation assays, in vivo skin equivalent grafting Molecular therapy High 30122422
2019 LAMB3 inhibition in pancreatic ductal adenocarcinoma cells abrogates PI3K/AKT pathway activation, causing cell cycle arrest and apoptosis, and reduces proliferation, invasion, migration, tumor growth, and liver metastasis in vivo. siRNA knockdown, cell cycle analysis, apoptosis assays, invasion/migration assays in vitro, xenograft and liver metastasis models in vivo, Western blot for PI3K/AKT pathway Cell death & disease Medium 30850586
2020 LAMB3 transcription in colorectal cancer is directly regulated by the BRD2/acetylated-ELK4 complex: ELK4 (acetylated at K125) cooperates with BRD2 to bind ETS motifs in the LAMB3 promoter; BET inhibitor JQ1 disrupts the ELK4-BRD2 interaction and reduces BRD2 binding to the LAMB3 promoter, downregulating LAMB3. Downstream, LAMB3 activates AKT to inhibit FOXO3/4 tumor-suppressive function. ChIP assay, luciferase reporter assays for promoter binding, Co-IP for ELK4-BRD2 interaction, JQ1/U0126 inhibitor treatment, Western blot, in vitro and in vivo tumor models Oncogene High 32398865
2020 miR-24-3p directly targets the LAMB3 3'UTR to suppress LAMB3 expression in pancreatic ductal adenocarcinoma cells; overexpression of miR-24-3p inhibits PDAC proliferation, cell cycle progression, and invasion by suppressing LAMB3, and this was confirmed in a xenograft model. Dual-luciferase reporter assay targeting LAMB3 3'UTR, FISH for subcellular localization of miR-24-3p and LAMB3 mRNA, rescue assays, subcutaneous xenograft Frontiers in oncology Medium 32039003
2022 S100A10 activates LAMB3 expression through the JNK pathway in pancreatic ductal adenocarcinoma; LAMB3 was shown to physically interact with LAMC2, and LAMB3 mediates the effects of S100A10 on cell proliferation, migration, and adhesion. RNA-sequencing, Western blotting, co-immunoprecipitation for LAMB3-LAMC2 interaction, JNK pathway inhibition, knockdown/overexpression rescue experiments, orthotopic tumor model Cancers Medium 36612197
2022 PIGR physically associates with the transcriptional repressor REST and blocks REST-mediated transcription of LAMB3 in colorectal cancer; PIGR overexpression downregulates LAMB3, suppressing the AKT-FOXO3/4 axis and inhibiting CRC cell malignant phenotypes. Co-immunoprecipitation of PIGR-REST complex, Western blot, in vitro functional assays, in vivo xenograft Frontiers in oncology Medium 35992840
2023 LAMB3 promotes intestinal inflammation through upregulation of SERPINA3 via the integrin α3β1/FAK pathway; NF-κB (P65) directly transcriptionally activates LAMB3 under TNF-α stimulation, as demonstrated by dual-luciferase assays and ChIP-PCR. Dual-luciferase assay, ChIP-PCR, RNA-sequencing, qRT-PCR, Western blotting, NF-κB inhibitor treatment Inflammatory bowel diseases High 37454278
2023 LAMB3 knockdown in nasopharyngeal carcinoma cells promotes apoptosis and reduces radioresistance by enhancing FOXO3 expression and thereby deactivating the NRF2 signaling pathway, leading to increased ROS accumulation after X-ray treatment. shRNA knockdown, ROS measurement, Western blot for NRF2/FOXO3 pathway, rescue experiments with NRF2 suppression, in vivo xenograft irradiation model Journal of radiation research Medium 36947579
2023 LAMB3 promotes myofibrogenesis and cytoskeletal reorganization in endometrial stromal cells via the RhoA/ROCK1/MYL9 pathway; LAMB3 overexpression promotes TGF-β-induced myofibroblast phenotype conversion and actin cytoskeleton remodeling, while LAMB3 silencing reverses these effects, and both are abrogated by the ROCK inhibitor Y-27632 or the RhoA activator LPA. LAMB3 overexpression and knockdown in primary endometrial stromal cells, PCR, Western blot, phalloidin staining for actin cytoskeleton, pharmacological inhibition/activation of RhoA/ROCK pathway Cell biochemistry and biophysics Medium 37801199
2024 NAT10 enhances LAMB3 mRNA stability via N4-acetylcytidine (ac4C) modification of LAMB3 mRNA; stabilized LAMB3 then activates the FAK/ERK pathway to promote PDAC tumor progression and upregulate PD-L1 expression, reducing CD8+ T cell cytotoxicity. Acetylated RNA immunoprecipitation (acRIP), qPCR, RNA immunoprecipitation, Western blotting, single-cell RNA sequencing, multiplexed immunofluorescence, flow cytometry, in vivo mouse models Cancer communications High 40540648
2024 FOXQ1, stabilized by PARP1 (via inhibition of E3 ubiquitin ligase CHIP-mediated degradation), directly binds the LAMB3 promoter region to activate LAMB3 transcription, which in turn activates the WNT/β-catenin signaling pathway to promote ovarian cancer progression. Co-IP, mass spectrometry, ubiquitination assays, ChIP-seq, ChIP-PCR, luciferase assays, RNA-seq, GSEA, Western blot, in vivo animal models Oncogene High 38297082
2024 MDFI directly interacts with LAMB3 (and ITGB4) in colorectal cancer cells, as confirmed by co-immunoprecipitation; MDFI upregulates the AKT pathway via its binding to LAMB3/ITGB4, enhancing CRC cell proliferation and reducing sensitivity to oxaliplatin and fluorouracil. Single-cell RNA sequencing, co-immunoprecipitation for MDFI-LAMB3/ITGB4 interaction, knockdown and lentiviral overexpression, Western blot, colony formation and CCK-8 assays Cancer biology & therapy Medium 38375821
2024 LAMB3 mediates gemcitabine resistance in PDAC through a YAP-LAMB3 feedback axis: YAP activates LAMB3 transcription via TEAD4, and LAMB3 in turn amplifies YAP signaling; this axis drives epithelial-mesenchymal transition and Gem resistance. Knockdown and overexpression experiments, in vitro drug sensitivity assays, Western blot for YAP/TEAD4/EMT markers, in vivo xenograft model Molecular carcinogenesis Medium 39016677
2024 LAMB3 knockdown decreases CXCL2 expression, reduces cancer-associated fibroblast (CAF) infiltration, and increases olaparib sensitivity in triple-negative breast cancer; melatonin downregulates LAMB3, and the LAMB3-CXCL2 axis was found to collaboratively promote CAF infiltration and immunosuppression. RNA-sequencing, genetic ablation (LAMB3 knockdown), Western blot, in vivo tumor models with combination treatment, immune cell profiling Pharmacological research Medium 39306019
2024 CRABP2 upregulates LAMB3 mRNA and protein expression (shown by RNA-seq and Western blot), and LAMB3 in turn activates the PI3K/AKT and MAPK signaling pathways to promote cell migration and invasion in prostate cancer. RNA-seq after CRABP2 overexpression, Western blot for LAMB3 and downstream pathway proteins, migration/invasion assays, in vivo tumor model Journal of biochemistry Medium 39038078
2024 An intronic LAMB3 variant (c.-38+2 T>C) activates a cryptic splice site, causing 120 bp intronic inclusion in the 5'UTR; this creates upstream AUGs and uORFs and a more complex 5'UTR secondary structure, significantly reducing translation efficiency of LAMB3 without affecting overall mRNA levels, causing JEB. Whole-exome and whole-genome sequencing, luciferase translational efficiency assays, splice assay (minigene), in silico structural analysis, RT-PCR on patient gingival sample Archives of oral biology High 39357391
2025 TGF-β secreted by hypoxic renal tubular epithelial cells activates canonical Smad signaling in fibroblasts, which upregulates LAMB3 expression via enhanced chromatin accessibility at the LAMB3 promoter; LAMB3 then initiates PI3K/AKT-dependent myofibroblast differentiation and renal fibrosis. Kidney-targeted knockdown of LAMB3 significantly ameliorates hypoxia-induced renal fibrosis in mice. ATAC-seq and RNA-seq (integrated), in vivo kidney-targeted LAMB3 knockdown, N-acetylcysteine (ROS scavenger) treatment, Western blot for Smad/AKT signaling, mouse hypoxic fibrosis model Free radical biology & medicine High 41412528
2023 Ribosomal protein L35/uL29 (RpL35) ligands artesunate and atazanavir selectively increase production of full-length LAMB3 protein from PTC-containing mRNA via ribosome editing (targeted readthrough enhancement), producing up to 200% increase in full-length LAMB3 without affecting an unrelated PTC reporter. Dual luciferase reporter assays with LAMB3 PTC constructs vs. unrelated PTC reporter, drug treatment with artesunate and atazanavir JID innovations Medium 38282649
2023 SOX10 deficiency in MAPK inhibitor-resistant melanoma cells drives LAMB3 upregulation through TGF-β signaling; elevated LAMB3 activates integrin α3/α6 signaling and a FAK/MMPs axis to promote migration and invasion; LAMB3 depletion inhibits metastatic potential of MAPKi-resistant cells in a mouse lung metastasis model. Transcriptome profiling, Western blot, siRNA knockdown, migration/invasion assays, in vivo lung metastasis mouse model Oncogene Medium 38102338
2026 Tumor-derived LAMB3 promotes LRRC15+ fibroblast differentiation in PDAC through the ITGB1/FAK/MAPK signaling axis, leading to FOSL2-dependent transcriptional activation of LRRC15 in fibroblasts and suppression of T cell cytotoxicity; FAK inhibition partially reverses these effects and LAMB3 knockdown improves PD-1 blockade efficacy. Single-cell atlas, functional assays (overexpression/knockdown), orthotopic mouse models, FAK inhibition, ChIP/transcriptome analysis for FOSL2-LRRC15 Advanced science Medium 42154006
2026 LAMB3 overexpression in keratinocytes upregulates cytokeratin expression and accelerates wound healing in vivo; the LAMB3-ITGA6 axis coordinates epithelial adhesion (hemidesmosome-associated gene activation) and keratinization in gingival epithelial repair, with retinoic acid reciprocally regulating this axis. Single-cell RNA sequencing, LAMB3 knockdown and overexpression (lentivirus), phalloidin staining, in vivo mouse dorsal wound healing model, retinol/BMS493 treatment Frontiers in cell and developmental biology Medium 41960183

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 A homozygous nonsense mutation in the beta 3 chain gene of laminin 5 (LAMB3) in Herlitz junctional epidermolysis bullosa. Genomics 196 7698759
2019 LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway. Cell death & disease 143 30850586
1995 Altered laminin 5 expression due to mutations in the gene encoding the beta 3 chain (LAMB3) in generalized atrophic benign epidermolysis bullosa. The Journal of investigative dermatology 113 7706760
1996 Mutational hotspots in the LAMB3 gene in the lethal (Herlitz) type of junctional epidermolysis bullosa. Human molecular genetics 87 8824879
2013 Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer. PloS one 78 23441154
1997 IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mammalian genome : official journal of the International Mammalian Genome Society 76 9271670
1997 Maternal uniparental disomy of chromosome 1 with reduction to homozygosity of the LAMB3 locus in a patient with Herlitz junctional epidermolysis bullosa. American journal of human genetics 75 9326326
2007 Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3. The Journal of clinical investigation 72 17476356
1999 Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes. American journal of human genetics 66 10577906
1995 Identification of a homozygous one-basepair deletion in exon 14 of the LAMB3 gene in a patient with Herlitz junctional epidermolysis bullosa and prenatal diagnosis in a family at risk for recurrence. The Journal of investigative dermatology 64 7706759
1995 Detection of sequence variants in the gene encoding the beta 3 chain of laminin 5 (LAMB3). Human mutation 61 7550237
1995 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. FEBS letters 58 7635220
2013 Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta. European journal of human genetics : EJHG 57 23632796
2020 LAMB3 promotes tumour progression through the AKT-FOXO3/4 axis and is transcriptionally regulated by the BRD2/acetylated ELK4 complex in colorectal cancer. Oncogene 56 32398865
2011 Aberrant up-regulation of LAMB3 and LAMC2 by promoter demethylation in gastric cancer. Biochemical and biophysical research communications 56 21345334
2010 Polymorphisms involved in the miR-218-LAMB3 pathway and susceptibility of cervical cancer, a case-control study in Chinese women. Gynecologic oncology 55 20163849
2018 Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa. Proceedings of the National Academy of Sciences of the United States of America 54 29946029
1995 Cloning of the beta 3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa. Genomics 54 7774918
2018 CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient. Molecular therapy : the journal of the American Society of Gene Therapy 52 30122422
2013 LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta. Journal of dental research 50 23958762
2015 High Diagnostic Accuracy Based on CLDN10, HMGA2, and LAMB3 Transcripts in Papillary Thyroid Carcinoma. The Journal of clinical endocrinology and metabolism 49 25867809
2016 miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3. Cancer research 48 27698189
2018 LAMB3 mediates metastatic tumor behavior in papillary thyroid cancer by regulating c-MET/Akt signals. Scientific reports 42 29426928
2008 Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 41 18331784
2000 Herlitz junctional epidermolysis bullosa: novel and recurrent mutations in the LAMB3 gene and the population carrier frequency. The Journal of investigative dermatology 37 11023379
2013 The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer. Clinics (Sao Paulo, Brazil) 31 23778407
1997 Predominance of the recurrent mutation R635X in the LAMB3 gene in European patients with Herlitz junctional epidermolysis bullosa has implications for mutation detection strategy. The Journal of investigative dermatology 31 9242513
2018 LAMB3 is associated with disease progression and cisplatin cytotoxic sensitivity in head and neck squamous cell carcinoma. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 28 30414703
2017 Upregulated LAMB3 increases proliferation and metastasis in thyroid cancer. OncoTargets and therapy 28 29317832
1998 Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa. The Journal of investigative dermatology 28 9579554
2020 MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation. Frontiers in oncology 27 32039003
1998 Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa. Biochemical and biophysical research communications 26 9501007
1996 Compound heterozygosity for nonsense ans missense mutations in the LAMB3 gene in nonlethal junctional epidermolysis bullosa. The Journal of investigative dermatology 26 8618058
2018 Identification of likely pathogenic and known variants in TSPEAR, LAMB3, BCOR, and WNT10A in four Turkish families with tooth agenesis. Human genetics 24 30046887
2000 Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas. Biochemical and biophysical research communications 24 10964684
2020 LncRNA DDX11-AS1 Promotes Bladder Cancer Occurrence Via Protecting LAMB3 from Downregulation by Sponging miR-2355-5p. Cancer biotherapy & radiopharmaceuticals 23 32412777
2015 Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta. PloS one 22 25769099
1996 Compound heterozygosity for nonsense and missense mutations in the LAMB3 gene in nonlethal junctional epidermolysis bullosa. The Journal of investigative dermatology 22 8618020
2006 Evaluation of prenatal intra-amniotic LAMB3 gene delivery in a mouse model of Herlitz disease. Gene therapy 21 16871230
2022 S100A10 Promotes Pancreatic Ductal Adenocarcinoma Cells Proliferation, Migration and Adhesion through JNK/LAMB3-LAMC2 Axis. Cancers 20 36612197
2017 The root of Actinidia chinensis inhibits hepatocellular carcinomas cells through LAMB3. Cell biology and toxicology 20 29127567
2024 PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway. Oncogene 19 38297082
2004 Analysis of the LAMB3 gene in a junctional epidermolysis bullosa patient reveals exonic splicing and allele-specific nonsense-mediated mRNA decay. Laboratory investigation; a journal of technical methods and pathology 19 15311214
1998 Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing. The Journal of investigative dermatology 19 9457915
1998 LAMB3 mutations in generalized atrophic benign epidermolysis bullosa: consequences at the mRNA and protein levels. Laboratory investigation; a journal of technical methods and pathology 19 9690563
1998 E210K mutation in the gene encoding the beta3 chain of laminin-5 (LAMB3) is predictive of a phenotype of generalized atrophic benign epidermolysis bullosa. The British journal of dermatology 19 9767254
2016 Whole-Exome Sequencing Suggests LAMB3 as a Susceptibility Gene for Morbid Obesity. Diabetes 16 27431458
2023 Tumor-derived extracellular vesicles delivering TNF-α promotes colorectal cancer metastasis via the NF-kB/LAMB3/AKT axis by targeting SNAP23. Archives of biochemistry and biophysics 13 37086961
2016 A unique LAMB3 splice-site mutation with founder effect from the Balkans causes lethal epidermolysis bullosa in several European countries. The British journal of dermatology 13 27062385
2016 A novel de novo mutation in LAMB3 causes localized hypoplastic enamel in the molar region. European journal of oral sciences 13 27220909
2024 The LAMB3-EGFR signaling pathway mediates synergistic Anti-Cancer effects of berberine and emodin in Pancreatic cancer. Biochemical pharmacology 12 39214450
2024 Melatonin increases Olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC. Pharmacological research 12 39306019
2022 Polymeric immunoglobulin receptor suppresses colorectal cancer through the AKT-FOXO3/4 axis by downregulating LAMB3 expression. Frontiers in oncology 12 35992840
2025 NAT10 regulates tumor progression and immune microenvironment in pancreatic ductal adenocarcinoma via the N4-acetylated LAMB3-mediated FAK/ERK pathway. Cancer communications (London, England) 11 40540648
2023 Multi-omics analysis of LAMB3 as a potential immunological and biomarker in pan-cancer. Frontiers in molecular biosciences 11 37577750
2024 MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway. Cancer biology & therapy 10 38375821
2022 hsa-mir-133a-2 promotes the proliferation and invasion of cervical cancer cells by targeting the LAMB3-mediated PI3K/ATK pathway. Cancer medicine 10 36305754
2024 LAMB3 Promotes Intestinal Inflammation Through SERPINA3 and Is Directly Transcriptionally Regulated by P65 in Inflammatory Bowel Disease. Inflammatory bowel diseases 9 37454278
2005 [Dental alterations in junctional epidermolysis bullosa--report of a patient with a mutation in the LAMB3-gene]. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 9 16372803
2024 CRABP2 promotes cell migration and invasion by activating PI3K/AKT and MAPK signalling pathways via upregulating LAMB3 in prostate cancer. Journal of biochemistry 8 39038078
2024 LAMB3: Central role and clinical significance in neoplastic and non-neoplastic diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 8 39111076
2020 LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa. Genes 8 32906717
2023 Knockdown of LAMB3 suppressed radioresistance in nasopharyngeal carcinoma via deactivating NRF2 signaling pathway. Journal of radiation research 7 36947579
1998 Molecular basis of non-lethal junctional epidermolysis bullosa: identification of a 38 basepair insertion and a splice site mutation in exon 14 of the LAMB3 gene. Experimental dermatology 7 9583749
2023 LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway. Cell biochemistry and biophysics 6 37801199
1998 Laminin 5 genes and Herlitz junctional epidermolysis bullosa: novel mutations and polymorphisms in the LAMB3 and LAMC2 genes. Mutations in brief no. 190. Online. Human mutation 6 10660342
2024 Downregulation of LAMB3 Altered the Carcinogenic Properties of Human Papillomavirus 16-Positive Cervical Cancer Cells. International journal of molecular sciences 5 38473784
2022 Identification of a novel homozygous LAMB3 mutation in a Chinese male with junctional epidermolysis bullosa and severe urethra stenosis: A case report. Frontiers in genetics 4 36246619
2012 Herlitz junctional epidermolysis bullosa with a novel mutation in LAMB3. Pediatric dermatology 4 23278291
2000 Compound heterozygosity for a point mutation and a deletion located at splice acceptor sites in the LAMB3 gene leads to generalized atrophic benign epidermolysis bullosa. The Journal of investigative dermatology 4 10951252
2024 Single-cell sequencing reveals increased LAMB3-positive basal keratinocytes and ZNF90-positive fibroblasts in autologous cultured epithelium. Communications biology 3 38200141
2023 En Route to Targeted Ribosome Editing to Replenish Skin Anchor Protein LAMB3 in Junctional Epidermolysis Bullosa. JID innovations : skin science from molecules to population health 3 38282649
2021 Decreased Expression of LAMB3 Is Associated with Esophageal Cancer Stem Cell Formation. Advanced pharmaceutical bulletin 3 36415640
2018 Targeted next-generation sequencing identifies a novel mutation of LAMB3 in a Chinese neonatal patient presented with junctional epidermolysis bullosa. Medicine 3 30544381
2023 Recessive COL17A1 Mutations and a Dominant LAMB3 Mutation Cause Hypoplastic Amelogenesis Imperfecta. Journal of personalized medicine 2 37888105
2023 SOX10 deficiency-mediated LAMB3 upregulation determines the invasiveness of MAPKi-resistant melanoma. Oncogene 2 38102338
2022 Corrigendum: Polymeric immunoglobulin receptor suppresses colorectal cancer through the AKT-FOXO3/4 axis by downregulating LAMB3 expression. Frontiers in oncology 2 36072792
2022 A novel splice-site variant of the LAMB3 gene is associated with junctional epidermolysis bullosa. European journal of dermatology : EJD 2 36468719
2025 A homozygous LAMB3 frameshift variant in junctional epidermolysis bullosa-affected Bleu du Maine sheep. Journal of applied genetics 1 40100311
2022 Modified Non-Cultured Cell Spray Induced Epithelization in LAMB3 Mutation Epidermolysis Bullosa. Clinical, cosmetic and investigational dermatology 1 36267689
2022 Rare compound heterozygous variants of LAMB3 and histological features of enamel and oral mucosa. Frontiers in physiology 1 36299258
1997 Identification of the LAMB3 hotspot mutation R635X in a Hungarian case of Herlitz junctional epidermolysis bullosa. Experimental dermatology 1 9209887
2026 A Case of Neonatal Junctional Epidermolysis Bullosa With a LAMB3 Mutation: Diagnostic Journey and Interdisciplinary Management. Case reports in pediatrics 0 41728083
2026 The LAMB3-ITGA6 axis orchestrates epithelial repair in periodontitis via hemidesmosomal regulation and keratinization modulation. Frontiers in cell and developmental biology 0 41960183
2026 Single-cell Analysis Reveals a LAMB3-dependent Immunosuppressive Environment in Gallbladder Neck/Cystic Duct Carcinoma. JHEP reports : innovation in hepatology 0 42002036
2026 Tumor-Derived LAMB3 Drives Immunosuppressive LRRC15+ Fibroblast Formation During Pancreatic Ductal Adenocarcinoma Development. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42154006
2025 Full-length transcriptome analysis of papillary thyroid carcinoma reveals correlation between LAMB3 expression and clinical features. BMC cancer 0 41139196
2025 TGF-β/LAMB3 axis drives ROS-dependent renal fibrosis under hypoxic conditions. Free radical biology & medicine 0 41412528
2025 Ophthalmic phenotype associated with a novel mutation in LAMB3 gene linked to uncommon Intermediate Junctional Epidermolysis Bullosa. American journal of ophthalmology case reports 0 41492568
2024 YAP-LAMB3 axis dictates cellular resistance of pancreatic ductal adenocarcinoma cells to gemcitabine. Molecular carcinogenesis 0 39016677
2024 An intronic variant in LAMB3 contributes to junctional epidermolysis bullosa and enamel hypoplasia via translational attenuation. Archives of oral biology 0 39357391
2022 Junctional epidermolysis bullosa with extensive lung involvement in three patients with a LAMB3 Mutation. Pediatric dermatology 0 35178765

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