{"gene":"ITGA3","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":1990,"finding":"ITGA3 (Gap-B3) was identified as a member of the integrin superfamily by cDNA cloning and amino acid sequencing. The protein consists of two polypeptide chains (Mr=110,000 and 30,000) connected by disulfide bonds, derived from a precursor by proteolytic cleavage, and contains metal-binding sequences, a transmembrane domain near C-terminus, and matched cysteine residue positions characteristic of integrin alpha subunits.","method":"cDNA cloning, protein purification, partial amino acid sequencing, Southern/Northern hybridization","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct protein purification to homogeneity, full cDNA cloning with sequence analysis, multiple orthogonal methods in a single foundational study","pmids":["1691184"],"is_preprint":false},{"year":2013,"finding":"Exosomal ITGA3 from prostate cancer cells promotes migration and invasion of non-cancerous prostate epithelial cells (prEC); inhibition of exosomal ITGA3 almost completely abolished this effect, establishing a paracrine/exosomal mechanism by which ITGA3 remodels surrounding non-cancerous cells.","method":"Exosome isolation by ultracentrifugation, transwell migration/invasion assay, LC-MS/MS proteomics, Western blotting, FACS uptake assay, ITGA3 inhibition","journal":"Journal of extracellular vesicles","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional inhibition experiment with defined phenotypic readout, proteomics validation, single lab with two orthogonal methods","pmids":["24371517"],"is_preprint":false},{"year":2015,"finding":"ITGA3 and ITGB1 are direct targets of miR-223 in prostate cancer cells; knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion, placing ITGA3 downstream of miR-223 in a signaling axis controlling cell motility.","method":"miRNA restoration, siRNA knockdown, in silico database analysis, genome-wide gene expression, transwell migration/invasion assays","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — siRNA knockdown with phenotypic readout, miRNA targeting inferred from expression analysis, single lab","pmids":["26509963"],"is_preprint":false},{"year":2017,"finding":"ITGA3 is a direct target of all members of the miR-199 family (miR-199a-5p, miR-199a-3p, miR-199b-5p, miR-199b-3p) in head and neck squamous cell carcinoma; knockdown of ITGA3 significantly inhibited cancer cell migration and invasion.","method":"Ectopic miRNA expression, in silico database and genome-wide gene expression analyses, siRNA knockdown, transwell migration/invasion assays","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — siRNA knockdown with phenotypic readout, multiple miRNA members validated, single lab","pmids":["28612520"],"is_preprint":false},{"year":2017,"finding":"ITGA3 is a validated target of miR-101 in nasopharyngeal carcinoma; ITGA3 restoration rescued the suppressive effects of miR-101 on migration, invasion, and angiogenesis in vitro and metastasis in vivo using the chicken chorioallantoic membrane model.","method":"Ectopic miRNA expression, ITGA3 rescue experiment, in vitro migration/invasion assays, in vivo chorioallantoic membrane angiogenesis/metastasis model","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo rescue experiment plus in vitro functional assays, single lab with multiple orthogonal methods","pmids":["28102841"],"is_preprint":false},{"year":2017,"finding":"In the developing inner ear, miR-183 directly represses ItgA3; this miR-183/ItgA3 axis controls cell proliferation in the developing cochlea, and loss of Dicer (impairing miRNA biogenesis) leads to failure of cochlear progenitors to exit the cell cycle, a phenotype linked to ItgA3 accumulation.","method":"Conditional Dicer knockout in otocyst, miRNA target identification, unbiased genomic approach","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function in vivo with specific proliferation phenotype, single lab","pmids":["28777373"],"is_preprint":false},{"year":2018,"finding":"ITGA3 and ITGB1 are directly regulated by miR-124-3p in pancreatic ductal adenocarcinoma cells (validated by luciferase reporter assay); knockdown of ITGA3/ITGB1 suppressed migration and invasion and inhibited phosphorylation of FAK, AKT, and ERK, placing ITGA3 upstream of these oncogenic signaling pathways.","method":"Luciferase reporter assay, siRNA knockdown, transwell migration/invasion assays, Western blot for phospho-FAK/AKT/ERK","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase validation of direct targeting plus downstream signaling readout, single lab with multiple orthogonal methods","pmids":["29988949"],"is_preprint":false},{"year":2018,"finding":"ITGA3 is a direct target of miR-124 in colorectal cancer (experimentally validated); ITGA3 plays a critical role in regulating anoikis sensitivity of CRC cells, with ITGA3 expression promoting anoikis resistance and facilitating metastasis in vivo.","method":"In silico analysis, experimental target validation, overexpression/knockdown functional assays, in vivo anoikis/metastasis assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo and in vitro functional validation, single lab","pmids":["29758195"],"is_preprint":false},{"year":2019,"finding":"miR-124-3p directly targets ITGA3 in bladder cancer (confirmed by luciferase reporter assay); ITGA3 knockdown inhibited tumor cell migration and invasion, and ITGA3 mediates its effects through FAK/PI3K/AKT and FAK/Src signaling pathways and modulation of EMT markers (N- and E-cadherin).","method":"Luciferase reporter assay, siRNA knockdown, wound healing and transwell assays, Western blot for FAK/PI3K/AKT/Src pathway proteins and EMT markers","journal":"Cancer biomarkers","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase direct target validation with downstream signaling pathway characterization, single lab, multiple methods","pmids":["30614803"],"is_preprint":false},{"year":2019,"finding":"miR-524-5p directly targets ITGA3 in papillary thyroid cancer (experimentally validated); downregulation of ITGA3 by miR-524-5p disturbs the autophagy pathway, inhibiting cancer cell viability, migration, invasion, and apoptosis.","method":"Direct target validation, functional cell viability/migration/invasion assays, pathway analysis","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct target validation with autophagy pathway link, single lab","pmids":["30941771"],"is_preprint":false},{"year":2020,"finding":"ITGA3 interacts with VASP in breast cancer cells (confirmed by co-immunoprecipitation and immunofluorescence); ITGA3 regulates VASP expression, and the ITGA3-VASP complex modulates breast cancer cell stemness, EMT, and PI3K-AKT pathway activity.","method":"Co-immunoprecipitation, immunofluorescence, Western blot, sphere formation assay, transwell and wound healing assays","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP identifying ITGA3-VASP interaction with downstream functional readouts, single lab","pmids":["31987909"],"is_preprint":false},{"year":2021,"finding":"CD9 and ITGA3 are upregulated in macrophages upon HIV-1 infection; downregulation of these genes decreased HIV-1 replication in macrophages, suggesting ITGA3 supports viral production most likely at the level of viral budding and release.","method":"Gene expression profiling, siRNA knockdown, viral replication assays in macrophages","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional knockdown with defined viral replication phenotype, single lab","pmids":["34242748"],"is_preprint":false},{"year":2022,"finding":"Transcription factor YY1 directly binds to the promoter region of ITGA3 and regulates its mRNA and protein expression in trophoblastic cells; both YY1 and ITGA3 accelerate phosphorylation of focal adhesion kinase (FAK) and affect cytoskeleton formation, modulating trophoblast invasion ability.","method":"ChIP-seq, RNA-seq, ChIP experiment, RT-PCR, dual-luciferase reporter gene assay, gene silencing, Western blot, immunofluorescence","journal":"Journal of reproductive immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and luciferase assays confirming direct transcriptional regulation, FAK phosphorylation and cytoskeletal readouts, single lab with multiple orthogonal methods","pmids":["35970081"],"is_preprint":false},{"year":2024,"finding":"Collagen I (Col1) secreted by pancreatic cancer cells acts as a ligand for ITGA3 in an autocrine manner, activating the FAK/PI3K/AKT/mTOR signaling pathway and thereby increasing expression of HIF1α and c-Myc to drive glycolysis; blockade of Col1 by siRNA or ITGA3 by a blocking antibody inactivated this pathway and impaired malignant tumor behaviors.","method":"Functional assays (growth, metastasis), siRNA knockdown of Col1, blocking antibody against ITGA3, Western blot for FAK/PI3K/AKT/mTOR/HIF1α/c-Myc, glycolysis assays","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ligand-receptor mechanism defined with two independent blockade approaches, downstream pathway characterization, single lab","pmids":["39690180"],"is_preprint":false},{"year":2024,"finding":"ITGA3 interacts with the MET receptor tyrosine kinase in papillary thyroid cancer (confirmed by co-immunoprecipitation and immunofluorescence); ITGA3-MET cooperation leads to MET phosphorylation at Tyr1234/1235 and activation of ERK and PI3K/AKT signaling pathways, promoting PTC proliferation and migration in vitro and in vivo.","method":"Co-immunoprecipitation, immunofluorescence, Western blot for MET phosphorylation and downstream pathway activation, cell functional assays, xenograft models","journal":"Annals of medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP identifying ITGA3-MET complex with downstream signaling and in vivo validation, single lab","pmids":["40138447"],"is_preprint":false},{"year":2024,"finding":"Iron accumulation elevates reactive oxygen species (ROS) which downregulates Itga3 expression in hippocampal neural stem cells (NSCs); reduced Itga3 leads to excessive NSC activation, depletion of the NSC pool, diminished neurogenesis, and cognitive dysfunction after intracerebral hemorrhage. Conditional overexpression of Itga3 in NSCs attenuated these defects.","method":"Mouse ICH model, iron chelation, ROS scavenging, conditional Itga3 overexpression in NSCs, neurogenesis assays, cognitive behavioral tests","journal":"Redox biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue experiment in vivo with defined mechanistic axis (ROS→Itga3→NSC pool), multiple pharmacological and genetic interventions, single lab","pmids":["38367510"],"is_preprint":false},{"year":2024,"finding":"ITGA3 knockdown in trophoblast cells suppresses ULK1 expression, impairing autophagy initiation and inhibiting trophoblast cell invasion and migration, contributing to recurrent spontaneous abortion pathology; ITGA3 regulates ULK1-mediated autophagy to influence trophoblast function.","method":"ITGA3 knockdown, RNA sequencing, ULK1 expression assays, autophagy assays, migration/invasion assays, mouse RSA model","journal":"American journal of physiology. Cell physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA-seq-guided mechanism, in vivo RSA model validation, single lab with multiple methods","pmids":["39437445"],"is_preprint":false},{"year":2024,"finding":"S100A16 binds to MOV10 (confirmed by co-immunoprecipitation) and positively modulates MOV10 expression in lung adenocarcinoma cells; MOV10 in turn stabilizes ITGA3 mRNA (confirmed by RNA immunoprecipitation and actinomycin D assay), regulating ECM-receptor interactions and promoting malignant progression.","method":"Co-immunoprecipitation (S100A16-MOV10), RNA immunoprecipitation (MOV10-ITGA3 mRNA), actinomycin D mRNA stability assay, knockdown/overexpression functional assays","journal":"Molecular medicine reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — protein-protein interaction and RNA-protein interaction confirmed by orthogonal methods, mRNA stability measured, single lab","pmids":["39450567"],"is_preprint":false},{"year":2024,"finding":"ITGA3 regulates AT2 cell self-renewal through the FAK/YAP axis in COPD; cigarette smoke-induced ROS accumulation suppresses ITGA3, leading to impaired FAK/YAP signaling and AT2 progenitor dysfunction; ROS scavenging with NAC restored ITGA3 expression, reactivated FAK/YAP signaling, and ameliorated emphysematous pathology.","method":"scRNA-seq, chronic CS-exposed murine model, alveolar organoids, ITGA3 genetic manipulation, pharmacological NAC intervention, immunostaining","journal":"Journal of advanced research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo and organoid genetic/pharmacological validation defining ROS/ITGA3/FAK/YAP axis, single lab with multiple orthogonal approaches","pmids":["41270956"],"is_preprint":false},{"year":2024,"finding":"ITGA3 is identified as a driver of early-stage lung adenocarcinoma in a KRAS-mutant AT2 injury/plasticity state; ITGA3 is co-expressed with SRC in AT2KRAS cells, and combined KRASG12D and SRC inhibitors impaired AT2KRAS organoid growth, placing ITGA3 in a KRAS-ITGA3-SRC signaling axis.","method":"scRNA-seq from organoids, mice, and stage-IA LUAD patients; KRASG12D and SRC inhibitor treatment of AT2 organoids","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multi-system scRNA-seq identification with pharmacological functional validation in organoids, single lab","pmids":["38755258"],"is_preprint":false},{"year":2025,"finding":"NPNT (nephronectin) interacts with ITGA3 and through this interaction inhibits LATS1/MOB1 hyperactivation, facilitates YAP1 nuclear translocation, and suppresses YAP1 ubiquitination and degradation, thereby regulating cellular senescence in alveolar epithelial cells and modulating pulmonary fibrosis.","method":"NPNT-ITGA3 interaction assays, YAP1 nuclear translocation imaging, ubiquitination assays, LATS1/MOB1 phosphorylation Western blot, NPNT overexpression/knockout mouse models, pharmacological Escin treatment","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic pathway defined with multiple orthogonal in vitro and in vivo methods, single lab","pmids":["40444575"],"is_preprint":false},{"year":2025,"finding":"ITGA3 is identified as a proximal interactor of the RPARPAR CendR peptide/NRP-1 receptor system; mass spectrometry of proximity-labeled membrane proteins from NRP-1-positive cells showed ~20-fold enrichment of ITGA3 (along with ITGAV and ITGB1), suggesting ITGA3 is in spatial proximity to the NRP-1 receptor complex at the cell surface.","method":"Proximity labeling with VHP-HRP conjugates, biotin-tyramide covalent labeling of nearby membrane proteins, affinity purification, mass spectrometry","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proximity labeling experiment (preprint), spatial proximity not equivalent to direct binding, single lab, no functional validation of ITGA3 specifically","pmids":[],"is_preprint":true},{"year":2025,"finding":"Integrin α3β1 (ITGA3/ITGB1) on pancreatic cancer cells is identified as a sialylated glycoprotein ligand for Siglec-10, an inhibitory glyco-immune checkpoint on tumor-associated macrophages; the Siglec-10/α3β1 interaction suppresses macrophage-mediated phagocytosis, and anti-Siglec-10 monoclonal antibodies disrupted this interaction and enhanced anti-tumor immunity in vitro and in mouse models.","method":"Ligand identification, monoclonal antibody blockade, macrophage phagocytosis assays, T cell proliferation assays, PDAC xenograft and human Siglec-10 transgenic mouse models","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — preprint with defined receptor-ligand interaction, in vitro and two in vivo models, multiple orthogonal assays, single lab","pmids":[],"is_preprint":true},{"year":2025,"finding":"SOX10 knockdown in melanoma upregulates ITGA3 (via IRF1 as an upstream regulator); ITGA3 is essential for cell adhesion and contributes to melanoma metastasis, acting downstream of SOX10-IRF1 in the SOX10-IRF1-ITGA3/EphA2-FAK pathway; FAK inhibitor defactinib significantly reduced metastasis in vivo.","method":"siRNA knockdown of SOX10, in silico and in vitro identification of ITGA3/EphA2 as downstream effectors, IRF1 identification as upstream regulator, FAK inhibitor treatment, in vivo metastasis assays","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis defining pathway position with in vivo pharmacological validation, single lab","pmids":["40808260"],"is_preprint":false},{"year":2025,"finding":"Rab3A directly targets and positively regulates ITGA3 expression (confirmed by dual luciferase assay); ITGA3 stabilization by Rab3A mediates protection against H2O2-induced oxidative stress and mitochondrial dysfunction in inner ear HEI-OC1 cells, as silencing ITGA3 reversed the protective effects of Rab3A.","method":"Dual luciferase assay, CCK-8 viability, flow cytometry apoptosis, immunofluorescence mitochondrial membrane potential, oxidative stress and mitochondrial function assays, siRNA knockdown of ITGA3","journal":"Journal of bioenergetics and biomembranes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase-validated direct regulation, functional rescue experiment, single lab","pmids":["41085878"],"is_preprint":false},{"year":2026,"finding":"ITGA3 on PDAC cells acts as a receptor for laminin-332 (LAM332) secreted by cancer-associated fibroblasts (CAFs); CAF-derived LAM332-ITGA3 engagement promotes PDAC cell proliferation, invasion, homotypic CTC clustering, and suppresses apoptosis; neutralization of LAM332 reduced hepatic/pulmonary metastasis and prolonged survival in mouse models.","method":"Proteomic and transcriptomic analyses, clinical specimen validation, LAM332 neutralization, CTC clustering assays, apoptosis assays, in vivo mouse metastasis models","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined ligand-receptor interaction with functional in vivo validation across multiple assays, single lab","pmids":["41881953"],"is_preprint":false},{"year":2026,"finding":"H. pylori infection induces p-STAT3 activation, which transcriptionally upregulates ITGA3; elevated ITGA3 then activates the NF-κB/mTOR signaling axis and enhances TGF-β-related signaling, promoting gastric cancer cell proliferation, EMT, and migration.","method":"H. pylori infection of GC cells, p-STAT3 pathway analysis, ITGA3 expression assays, NF-κB/mTOR and TGF-β pathway Western blots, functional proliferation/migration/EMT assays, in vivo tumor growth","journal":"Molecular and cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic pathway defined with transcriptional regulation and downstream signaling, in vitro and in vivo, single lab","pmids":["42240927"],"is_preprint":false}],"current_model":"ITGA3 is an integrin alpha subunit that forms a heterodimer (α3β1) acting as a cell-surface adhesion and signaling receptor for extracellular matrix ligands including laminin-332 and collagen I; ligand engagement activates FAK/PI3K/AKT/mTOR, ERK, and Src downstream cascades to regulate cell migration, invasion, EMT, anoikis resistance, glycolysis, and progenitor cell self-renewal, while ITGA3 also engages binding partners including VASP, MET, and Siglec-10, is transcriptionally regulated by YY1 and STAT3, post-transcriptionally controlled by multiple miRNAs (miR-223, miR-199 family, miR-101, miR-124/124-3p, miR-183, miR-524-5p, miR-144-5p), and has mRNA stability modulated via S100A16-MOV10; loss of ITGA3 impairs neural stem cell homeostasis, trophoblast invasion via the ULK1-autophagy axis, and alveolar epithelial progenitor self-renewal via FAK/YAP signaling."},"narrative":{"mechanistic_narrative":"ITGA3 is an integrin alpha subunit, derived by proteolytic cleavage into disulfide-linked heavy and light chains and bearing metal-binding motifs and a transmembrane segment characteristic of the integrin superfamily [PMID:1691184], that pairs with ITGB1 to form a cell-surface receptor coupling extracellular matrix engagement to migration, invasion, and progenitor cell behavior. As the α3β1 heterodimer it binds ECM ligands including autocrine collagen I and fibroblast-derived laminin-332, engagement of which drives FAK/PI3K/AKT/mTOR signaling to upregulate HIF1α/c-Myc-dependent glycolysis and to promote proliferation, invasion, and circulating-tumor-cell clustering [PMID:39690180, PMID:41881953]. Across cancer types ITGA3 acts upstream of FAK/PI3K/AKT, FAK/Src, and ERK cascades and modulates EMT markers to control motility and anoikis resistance [PMID:29988949, PMID:29758195, PMID:30614803]. It physically partners with VASP to regulate stemness and EMT [PMID:31987909] and cooperates with the MET receptor tyrosine kinase, promoting MET phosphorylation at Tyr1234/1235 and ERK and PI3K/AKT activation [PMID:40138447]. ITGA3 expression is transcriptionally controlled by YY1 in trophoblasts [PMID:35970081] and by STAT3 during H. pylori-driven gastric carcinogenesis [PMID:42240927], post-transcriptionally repressed by numerous miRNAs (miR-223, the miR-199 family, miR-101, miR-124/124-3p, miR-183, miR-524-5p) [PMID:26509963, PMID:28612520, PMID:28102841, PMID:30614803, PMID:28777373], and stabilized at the mRNA level via the S100A16-MOV10 axis [PMID:39450567]. Beyond cancer, ITGA3 supports tissue progenitor homeostasis: it sustains the hippocampal neural stem cell pool against ROS-driven depletion [PMID:38367510], drives ULK1-dependent autophagy to enable trophoblast invasion [PMID:39437445], and maintains alveolar AT2 progenitor self-renewal through FAK/YAP signaling, with NPNT engagement stabilizing YAP1 by restraining LATS1/MOB1 [PMID:41270956, PMID:40444575]. Sialylated α3β1 also functions as a ligand for the macrophage inhibitory checkpoint Siglec-10 to suppress phagocytosis.","teleology":[{"year":1990,"claim":"Established the molecular identity of ITGA3 as an integrin alpha subunit, defining the structural basis for its receptor function.","evidence":"cDNA cloning, protein purification, and partial amino acid sequencing","pmids":["1691184"],"confidence":"High","gaps":["Does not define the ligand specificity or signaling output of the protein","Heterodimer partner not functionally characterized in this study"]},{"year":2013,"claim":"Showed ITGA3 can act non-cell-autonomously, addressing whether the integrin contributes to tumor microenvironment remodeling beyond the cell expressing it.","evidence":"Exosome isolation, transwell assays, and ITGA3 inhibition in prostate cancer/prEC cells","pmids":["24371517"],"confidence":"Medium","gaps":["Molecular mechanism by which exosomal ITGA3 acts on recipient cells unresolved","Whether intact α3β1 or cleaved fragments mediate the effect not addressed"]},{"year":2015,"claim":"Placed ITGA3 within post-transcriptional regulatory circuits controlling motility, beginning the mapping of upstream miRNA control.","evidence":"miR-223 restoration and ITGA3/ITGB1 siRNA knockdown with migration/invasion assays in prostate cancer","pmids":["26509963"],"confidence":"Medium","gaps":["Direct binding inferred from expression rather than reporter assay","Downstream signaling not characterized here"]},{"year":2017,"claim":"Extended ITGA3 as a convergent miRNA target across head/neck, nasopharyngeal cancers and the developing cochlea, linking its dosage to proliferation and metastatic phenotypes.","evidence":"Ectopic miRNA expression, ITGA3 rescue, in vivo CAM metastasis model, and conditional Dicer knockout","pmids":["28612520","28102841","28777373"],"confidence":"Medium","gaps":["Tissue-specific selectivity among the many ITGA3-targeting miRNAs unresolved","Whether ITGA3 protein level alone is the rate-limiting effector not isolated"]},{"year":2018,"claim":"Defined the downstream signaling consequences of ITGA3, placing it upstream of FAK/AKT/ERK and as a regulator of anoikis sensitivity.","evidence":"Luciferase reporter validation of miR-124-3p, siRNA knockdown, phospho-FAK/AKT/ERK Western blots, in vivo anoikis/metastasis assays in PDAC and colorectal cancer","pmids":["29988949","29758195"],"confidence":"Medium","gaps":["The ECM ligand triggering these cascades not identified in these studies","Contribution of ITGB1 partner versus ITGA3 alone not separated"]},{"year":2019,"claim":"Connected ITGA3 to EMT-driving FAK/PI3K/AKT and FAK/Src pathways and to autophagy regulation, broadening its signaling repertoire.","evidence":"Luciferase reporter assays, knockdown, EMT marker and pathway Western blots in bladder and papillary thyroid cancer","pmids":["30614803","30941771"],"confidence":"Medium","gaps":["Mechanistic link between ITGA3 and autophagy machinery not defined at this stage","Direct versus indirect EMT regulation unresolved"]},{"year":2020,"claim":"Identified the first direct physical partner beyond the integrin beta chain, VASP, tying ITGA3 to cytoskeletal regulation of stemness.","evidence":"Reciprocal co-immunoprecipitation, immunofluorescence, sphere formation and migration assays in breast cancer","pmids":["31987909"],"confidence":"Medium","gaps":["Structural basis and stoichiometry of the ITGA3-VASP interaction unknown","Whether VASP binding is ligand-engagement dependent not tested"]},{"year":2021,"claim":"Implicated ITGA3 in viral biology, indicating a role at the membrane in HIV-1 production in macrophages.","evidence":"Gene expression profiling, siRNA knockdown, and viral replication assays in macrophages","pmids":["34242748"],"confidence":"Medium","gaps":["Mechanism at viral budding/release stage inferred but not directly demonstrated","Whether ITGA3 acts as adhesion receptor or scaffold in this context unknown"]},{"year":2022,"claim":"Established direct transcriptional control of ITGA3 by YY1 and linked the axis to FAK phosphorylation and cytoskeletal remodeling in trophoblast invasion.","evidence":"ChIP-seq, ChIP, dual-luciferase reporter, gene silencing, and immunofluorescence in trophoblastic cells","pmids":["35970081"],"confidence":"Medium","gaps":["Whether YY1 regulation operates outside trophoblasts not addressed","Upstream signals controlling YY1 in this context unresolved"]},{"year":2024,"claim":"Identified physiological ECM ligands and a receptor-tyrosine-kinase co-receptor, converting ITGA3 from an inferred adhesion molecule into a defined signaling receptor for collagen I and a MET partner driving glycolysis and proliferation.","evidence":"ITGA3 blocking antibody, Col1 siRNA, MET phospho-Western blots, glycolysis assays, co-IP, and xenografts in PDAC and papillary thyroid cancer","pmids":["39690180","40138447"],"confidence":"Medium","gaps":["Whether collagen I binds α3β1 directly or requires accessory factors not fully resolved","Structural interface of ITGA3-MET cooperation unknown"]},{"year":2024,"claim":"Demonstrated a tissue-protective progenitor-maintenance role for ITGA3 in neural and alveolar stem cells through ROS-sensitive FAK/YAP signaling and an autophagy/ULK1 axis in trophoblasts.","evidence":"Conditional Itga3 overexpression/knockdown, ICH and CS-exposed mouse models, alveolar organoids, RNA-seq, ULK1 assays, NAC intervention","pmids":["38367510","39437445","41270956","38755258"],"confidence":"Medium","gaps":["How ROS suppresses ITGA3 expression mechanistically unresolved","Whether ECM ligand engagement is required for progenitor maintenance not isolated"]},{"year":2024,"claim":"Revealed ITGA3 mRNA stability control by the S100A16-MOV10 axis, adding a post-transcriptional input distinct from miRNA repression.","evidence":"Co-IP (S100A16-MOV10), RNA immunoprecipitation (MOV10-ITGA3 mRNA), and actinomycin D stability assay in lung adenocarcinoma","pmids":["39450567"],"confidence":"Medium","gaps":["Sequence elements in ITGA3 mRNA bound by MOV10 not mapped","Generality across tissues unknown"]},{"year":2025,"claim":"Positioned ITGA3 in immune evasion and additional ECM/transcriptional circuits, identifying it as a Siglec-10 glyco-ligand, a SOX10-IRF1 effector, and a STAT3 target, and detailing NPNT-mediated YAP1 stabilization.","evidence":"Ligand identification, monoclonal antibody blockade, phagocytosis assays, genetic epistasis, FAK inhibitor and Escin treatments, NPNT mouse models, laminin-332 neutralization across PDAC, melanoma, gastric cancer and fibrosis","pmids":["40444575","40808260","41881953","42240927"],"confidence":"Medium","gaps":["Sialylation enzymes generating the Siglec-10 epitope on α3β1 not defined","Interplay between the many parallel ITGA3 axes within a single cell unresolved"]},{"year":null,"claim":"How the diverse ligand engagements, partner interactions, and transcriptional/post-transcriptional inputs are integrated into context-specific ITGA3 outputs, and the structural basis of its non-canonical partnerships, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of ITGA3 ligand or co-receptor interfaces in the corpus","No causative human Mendelian disease mutation documented in the timeline","Quantitative hierarchy among competing regulatory inputs unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[13,25,0]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[13,14,25]},{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[22]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,13,22]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[6,8,13,14]},{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[13,25]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[15,18,16]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[22,11]}],"complexes":["integrin alpha3beta1"],"partners":["ITGB1","VASP","MET","NPNT","MOV10","SIGLEC10"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P26006","full_name":"Integrin alpha-3","aliases":["CD49 antigen-like family member C","FRP-2","Galactoprotein B3","GAPB3","VLA-3 subunit alpha"],"length_aa":1051,"mass_kda":116.6,"function":"Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration (Microbial infection) Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression","subcellular_location":"Cell membrane; Cell membrane; Cell projection, invadopodium membrane; Cell projection, filopodium membrane","url":"https://www.uniprot.org/uniprotkb/P26006/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ITGA3","classification":"Not Classified","n_dependent_lines":106,"n_total_lines":1208,"dependency_fraction":0.08774834437086093},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ITGA3","total_profiled":1310},"omim":[{"mim_id":"614748","title":"EPIDERMOLYSIS BULLOSA, JUNCTIONAL 7, WITH INTERSTITIAL LUNG DISEASE AND NEPHROTIC SYNDROME; JEB7","url":"https://www.omim.org/entry/614748"},{"mim_id":"606994","title":"TYROSINE KINASE, NONRECEPTOR, 2; TNK2","url":"https://www.omim.org/entry/606994"},{"mim_id":"605025","title":"INTEGRIN, ALPHA-3; ITGA3","url":"https://www.omim.org/entry/605025"},{"mim_id":"603448","title":"DAB ADAPTOR PROTEIN 1; DAB1","url":"https://www.omim.org/entry/603448"},{"mim_id":"602243","title":"CD151 ANTIGEN; CD151","url":"https://www.omim.org/entry/602243"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ITGA3"},"hgnc":{"alias_symbol":["CD49c","VLA3a","VCA-2","GAP-B3"],"prev_symbol":["MSK18"]},"alphafold":{"accession":"P26006","domains":[{"cath_id":"2.130.10.130","chopping":"34-461","consensus_level":"high","plddt":92.985,"start":34,"end":461},{"cath_id":"2.60.40.1460","chopping":"465-610","consensus_level":"high","plddt":84.1029,"start":465,"end":610},{"cath_id":"2.60.40.1510","chopping":"624-758","consensus_level":"high","plddt":87.2451,"start":624,"end":758},{"cath_id":"2.60.40.1530","chopping":"763-856_897-979","consensus_level":"high","plddt":85.0989,"start":763,"end":979}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P26006","model_url":"https://alphafold.ebi.ac.uk/files/AF-P26006-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P26006-F1-predicted_aligned_error_v6.png","plddt_mean":83.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ITGA3","jax_strain_url":"https://www.jax.org/strain/search?query=ITGA3"},"sequence":{"accession":"P26006","fasta_url":"https://rest.uniprot.org/uniprotkb/P26006.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P26006/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P26006"}},"corpus_meta":[{"pmid":"24371517","id":"PMC_24371517","title":"Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients.","date":"2013","source":"Journal of extracellular vesicles","url":"https://pubmed.ncbi.nlm.nih.gov/24371517","citation_count":137,"is_preprint":false},{"pmid":"26509963","id":"PMC_26509963","title":"Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.","date":"2015","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/26509963","citation_count":129,"is_preprint":false},{"pmid":"28612520","id":"PMC_28612520","title":"Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer.","date":"2017","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/28612520","citation_count":112,"is_preprint":false},{"pmid":"30614803","id":"PMC_30614803","title":"MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer.","date":"2019","source":"Cancer biomarkers : section A of Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/30614803","citation_count":59,"is_preprint":false},{"pmid":"1691184","id":"PMC_1691184","title":"Characterization through cDNA cloning of galactoprotein b3 (Gap b3), a cell surface membrane glycoprotein showing enhanced expression on oncogenic transformation. 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The protein consists of two polypeptide chains (Mr=110,000 and 30,000) connected by disulfide bonds, derived from a precursor by proteolytic cleavage, and contains metal-binding sequences, a transmembrane domain near C-terminus, and matched cysteine residue positions characteristic of integrin alpha subunits.\",\n      \"method\": \"cDNA cloning, protein purification, partial amino acid sequencing, Southern/Northern hybridization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct protein purification to homogeneity, full cDNA cloning with sequence analysis, multiple orthogonal methods in a single foundational study\",\n      \"pmids\": [\"1691184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Exosomal ITGA3 from prostate cancer cells promotes migration and invasion of non-cancerous prostate epithelial cells (prEC); inhibition of exosomal ITGA3 almost completely abolished this effect, establishing a paracrine/exosomal mechanism by which ITGA3 remodels surrounding non-cancerous cells.\",\n      \"method\": \"Exosome isolation by ultracentrifugation, transwell migration/invasion assay, LC-MS/MS proteomics, Western blotting, FACS uptake assay, ITGA3 inhibition\",\n      \"journal\": \"Journal of extracellular vesicles\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional inhibition experiment with defined phenotypic readout, proteomics validation, single lab with two orthogonal methods\",\n      \"pmids\": [\"24371517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"ITGA3 and ITGB1 are direct targets of miR-223 in prostate cancer cells; knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion, placing ITGA3 downstream of miR-223 in a signaling axis controlling cell motility.\",\n      \"method\": \"miRNA restoration, siRNA knockdown, in silico database analysis, genome-wide gene expression, transwell migration/invasion assays\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — siRNA knockdown with phenotypic readout, miRNA targeting inferred from expression analysis, single lab\",\n      \"pmids\": [\"26509963\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"ITGA3 is a direct target of all members of the miR-199 family (miR-199a-5p, miR-199a-3p, miR-199b-5p, miR-199b-3p) in head and neck squamous cell carcinoma; knockdown of ITGA3 significantly inhibited cancer cell migration and invasion.\",\n      \"method\": \"Ectopic miRNA expression, in silico database and genome-wide gene expression analyses, siRNA knockdown, transwell migration/invasion assays\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — siRNA knockdown with phenotypic readout, multiple miRNA members validated, single lab\",\n      \"pmids\": [\"28612520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"ITGA3 is a validated target of miR-101 in nasopharyngeal carcinoma; ITGA3 restoration rescued the suppressive effects of miR-101 on migration, invasion, and angiogenesis in vitro and metastasis in vivo using the chicken chorioallantoic membrane model.\",\n      \"method\": \"Ectopic miRNA expression, ITGA3 rescue experiment, in vitro migration/invasion assays, in vivo chorioallantoic membrane angiogenesis/metastasis model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo rescue experiment plus in vitro functional assays, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"28102841\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In the developing inner ear, miR-183 directly represses ItgA3; this miR-183/ItgA3 axis controls cell proliferation in the developing cochlea, and loss of Dicer (impairing miRNA biogenesis) leads to failure of cochlear progenitors to exit the cell cycle, a phenotype linked to ItgA3 accumulation.\",\n      \"method\": \"Conditional Dicer knockout in otocyst, miRNA target identification, unbiased genomic approach\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function in vivo with specific proliferation phenotype, single lab\",\n      \"pmids\": [\"28777373\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ITGA3 and ITGB1 are directly regulated by miR-124-3p in pancreatic ductal adenocarcinoma cells (validated by luciferase reporter assay); knockdown of ITGA3/ITGB1 suppressed migration and invasion and inhibited phosphorylation of FAK, AKT, and ERK, placing ITGA3 upstream of these oncogenic signaling pathways.\",\n      \"method\": \"Luciferase reporter assay, siRNA knockdown, transwell migration/invasion assays, Western blot for phospho-FAK/AKT/ERK\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase validation of direct targeting plus downstream signaling readout, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"29988949\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ITGA3 is a direct target of miR-124 in colorectal cancer (experimentally validated); ITGA3 plays a critical role in regulating anoikis sensitivity of CRC cells, with ITGA3 expression promoting anoikis resistance and facilitating metastasis in vivo.\",\n      \"method\": \"In silico analysis, experimental target validation, overexpression/knockdown functional assays, in vivo anoikis/metastasis assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo and in vitro functional validation, single lab\",\n      \"pmids\": [\"29758195\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"miR-124-3p directly targets ITGA3 in bladder cancer (confirmed by luciferase reporter assay); ITGA3 knockdown inhibited tumor cell migration and invasion, and ITGA3 mediates its effects through FAK/PI3K/AKT and FAK/Src signaling pathways and modulation of EMT markers (N- and E-cadherin).\",\n      \"method\": \"Luciferase reporter assay, siRNA knockdown, wound healing and transwell assays, Western blot for FAK/PI3K/AKT/Src pathway proteins and EMT markers\",\n      \"journal\": \"Cancer biomarkers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase direct target validation with downstream signaling pathway characterization, single lab, multiple methods\",\n      \"pmids\": [\"30614803\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"miR-524-5p directly targets ITGA3 in papillary thyroid cancer (experimentally validated); downregulation of ITGA3 by miR-524-5p disturbs the autophagy pathway, inhibiting cancer cell viability, migration, invasion, and apoptosis.\",\n      \"method\": \"Direct target validation, functional cell viability/migration/invasion assays, pathway analysis\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct target validation with autophagy pathway link, single lab\",\n      \"pmids\": [\"30941771\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ITGA3 interacts with VASP in breast cancer cells (confirmed by co-immunoprecipitation and immunofluorescence); ITGA3 regulates VASP expression, and the ITGA3-VASP complex modulates breast cancer cell stemness, EMT, and PI3K-AKT pathway activity.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, Western blot, sphere formation assay, transwell and wound healing assays\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP identifying ITGA3-VASP interaction with downstream functional readouts, single lab\",\n      \"pmids\": [\"31987909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CD9 and ITGA3 are upregulated in macrophages upon HIV-1 infection; downregulation of these genes decreased HIV-1 replication in macrophages, suggesting ITGA3 supports viral production most likely at the level of viral budding and release.\",\n      \"method\": \"Gene expression profiling, siRNA knockdown, viral replication assays in macrophages\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional knockdown with defined viral replication phenotype, single lab\",\n      \"pmids\": [\"34242748\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Transcription factor YY1 directly binds to the promoter region of ITGA3 and regulates its mRNA and protein expression in trophoblastic cells; both YY1 and ITGA3 accelerate phosphorylation of focal adhesion kinase (FAK) and affect cytoskeleton formation, modulating trophoblast invasion ability.\",\n      \"method\": \"ChIP-seq, RNA-seq, ChIP experiment, RT-PCR, dual-luciferase reporter gene assay, gene silencing, Western blot, immunofluorescence\",\n      \"journal\": \"Journal of reproductive immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and luciferase assays confirming direct transcriptional regulation, FAK phosphorylation and cytoskeletal readouts, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"35970081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Collagen I (Col1) secreted by pancreatic cancer cells acts as a ligand for ITGA3 in an autocrine manner, activating the FAK/PI3K/AKT/mTOR signaling pathway and thereby increasing expression of HIF1α and c-Myc to drive glycolysis; blockade of Col1 by siRNA or ITGA3 by a blocking antibody inactivated this pathway and impaired malignant tumor behaviors.\",\n      \"method\": \"Functional assays (growth, metastasis), siRNA knockdown of Col1, blocking antibody against ITGA3, Western blot for FAK/PI3K/AKT/mTOR/HIF1α/c-Myc, glycolysis assays\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ligand-receptor mechanism defined with two independent blockade approaches, downstream pathway characterization, single lab\",\n      \"pmids\": [\"39690180\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ITGA3 interacts with the MET receptor tyrosine kinase in papillary thyroid cancer (confirmed by co-immunoprecipitation and immunofluorescence); ITGA3-MET cooperation leads to MET phosphorylation at Tyr1234/1235 and activation of ERK and PI3K/AKT signaling pathways, promoting PTC proliferation and migration in vitro and in vivo.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, Western blot for MET phosphorylation and downstream pathway activation, cell functional assays, xenograft models\",\n      \"journal\": \"Annals of medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP identifying ITGA3-MET complex with downstream signaling and in vivo validation, single lab\",\n      \"pmids\": [\"40138447\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Iron accumulation elevates reactive oxygen species (ROS) which downregulates Itga3 expression in hippocampal neural stem cells (NSCs); reduced Itga3 leads to excessive NSC activation, depletion of the NSC pool, diminished neurogenesis, and cognitive dysfunction after intracerebral hemorrhage. Conditional overexpression of Itga3 in NSCs attenuated these defects.\",\n      \"method\": \"Mouse ICH model, iron chelation, ROS scavenging, conditional Itga3 overexpression in NSCs, neurogenesis assays, cognitive behavioral tests\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue experiment in vivo with defined mechanistic axis (ROS→Itga3→NSC pool), multiple pharmacological and genetic interventions, single lab\",\n      \"pmids\": [\"38367510\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ITGA3 knockdown in trophoblast cells suppresses ULK1 expression, impairing autophagy initiation and inhibiting trophoblast cell invasion and migration, contributing to recurrent spontaneous abortion pathology; ITGA3 regulates ULK1-mediated autophagy to influence trophoblast function.\",\n      \"method\": \"ITGA3 knockdown, RNA sequencing, ULK1 expression assays, autophagy assays, migration/invasion assays, mouse RSA model\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA-seq-guided mechanism, in vivo RSA model validation, single lab with multiple methods\",\n      \"pmids\": [\"39437445\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"S100A16 binds to MOV10 (confirmed by co-immunoprecipitation) and positively modulates MOV10 expression in lung adenocarcinoma cells; MOV10 in turn stabilizes ITGA3 mRNA (confirmed by RNA immunoprecipitation and actinomycin D assay), regulating ECM-receptor interactions and promoting malignant progression.\",\n      \"method\": \"Co-immunoprecipitation (S100A16-MOV10), RNA immunoprecipitation (MOV10-ITGA3 mRNA), actinomycin D mRNA stability assay, knockdown/overexpression functional assays\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — protein-protein interaction and RNA-protein interaction confirmed by orthogonal methods, mRNA stability measured, single lab\",\n      \"pmids\": [\"39450567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ITGA3 regulates AT2 cell self-renewal through the FAK/YAP axis in COPD; cigarette smoke-induced ROS accumulation suppresses ITGA3, leading to impaired FAK/YAP signaling and AT2 progenitor dysfunction; ROS scavenging with NAC restored ITGA3 expression, reactivated FAK/YAP signaling, and ameliorated emphysematous pathology.\",\n      \"method\": \"scRNA-seq, chronic CS-exposed murine model, alveolar organoids, ITGA3 genetic manipulation, pharmacological NAC intervention, immunostaining\",\n      \"journal\": \"Journal of advanced research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo and organoid genetic/pharmacological validation defining ROS/ITGA3/FAK/YAP axis, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"41270956\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ITGA3 is identified as a driver of early-stage lung adenocarcinoma in a KRAS-mutant AT2 injury/plasticity state; ITGA3 is co-expressed with SRC in AT2KRAS cells, and combined KRASG12D and SRC inhibitors impaired AT2KRAS organoid growth, placing ITGA3 in a KRAS-ITGA3-SRC signaling axis.\",\n      \"method\": \"scRNA-seq from organoids, mice, and stage-IA LUAD patients; KRASG12D and SRC inhibitor treatment of AT2 organoids\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multi-system scRNA-seq identification with pharmacological functional validation in organoids, single lab\",\n      \"pmids\": [\"38755258\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NPNT (nephronectin) interacts with ITGA3 and through this interaction inhibits LATS1/MOB1 hyperactivation, facilitates YAP1 nuclear translocation, and suppresses YAP1 ubiquitination and degradation, thereby regulating cellular senescence in alveolar epithelial cells and modulating pulmonary fibrosis.\",\n      \"method\": \"NPNT-ITGA3 interaction assays, YAP1 nuclear translocation imaging, ubiquitination assays, LATS1/MOB1 phosphorylation Western blot, NPNT overexpression/knockout mouse models, pharmacological Escin treatment\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic pathway defined with multiple orthogonal in vitro and in vivo methods, single lab\",\n      \"pmids\": [\"40444575\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ITGA3 is identified as a proximal interactor of the RPARPAR CendR peptide/NRP-1 receptor system; mass spectrometry of proximity-labeled membrane proteins from NRP-1-positive cells showed ~20-fold enrichment of ITGA3 (along with ITGAV and ITGB1), suggesting ITGA3 is in spatial proximity to the NRP-1 receptor complex at the cell surface.\",\n      \"method\": \"Proximity labeling with VHP-HRP conjugates, biotin-tyramide covalent labeling of nearby membrane proteins, affinity purification, mass spectrometry\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proximity labeling experiment (preprint), spatial proximity not equivalent to direct binding, single lab, no functional validation of ITGA3 specifically\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Integrin α3β1 (ITGA3/ITGB1) on pancreatic cancer cells is identified as a sialylated glycoprotein ligand for Siglec-10, an inhibitory glyco-immune checkpoint on tumor-associated macrophages; the Siglec-10/α3β1 interaction suppresses macrophage-mediated phagocytosis, and anti-Siglec-10 monoclonal antibodies disrupted this interaction and enhanced anti-tumor immunity in vitro and in mouse models.\",\n      \"method\": \"Ligand identification, monoclonal antibody blockade, macrophage phagocytosis assays, T cell proliferation assays, PDAC xenograft and human Siglec-10 transgenic mouse models\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — preprint with defined receptor-ligand interaction, in vitro and two in vivo models, multiple orthogonal assays, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SOX10 knockdown in melanoma upregulates ITGA3 (via IRF1 as an upstream regulator); ITGA3 is essential for cell adhesion and contributes to melanoma metastasis, acting downstream of SOX10-IRF1 in the SOX10-IRF1-ITGA3/EphA2-FAK pathway; FAK inhibitor defactinib significantly reduced metastasis in vivo.\",\n      \"method\": \"siRNA knockdown of SOX10, in silico and in vitro identification of ITGA3/EphA2 as downstream effectors, IRF1 identification as upstream regulator, FAK inhibitor treatment, in vivo metastasis assays\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis defining pathway position with in vivo pharmacological validation, single lab\",\n      \"pmids\": [\"40808260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Rab3A directly targets and positively regulates ITGA3 expression (confirmed by dual luciferase assay); ITGA3 stabilization by Rab3A mediates protection against H2O2-induced oxidative stress and mitochondrial dysfunction in inner ear HEI-OC1 cells, as silencing ITGA3 reversed the protective effects of Rab3A.\",\n      \"method\": \"Dual luciferase assay, CCK-8 viability, flow cytometry apoptosis, immunofluorescence mitochondrial membrane potential, oxidative stress and mitochondrial function assays, siRNA knockdown of ITGA3\",\n      \"journal\": \"Journal of bioenergetics and biomembranes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase-validated direct regulation, functional rescue experiment, single lab\",\n      \"pmids\": [\"41085878\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ITGA3 on PDAC cells acts as a receptor for laminin-332 (LAM332) secreted by cancer-associated fibroblasts (CAFs); CAF-derived LAM332-ITGA3 engagement promotes PDAC cell proliferation, invasion, homotypic CTC clustering, and suppresses apoptosis; neutralization of LAM332 reduced hepatic/pulmonary metastasis and prolonged survival in mouse models.\",\n      \"method\": \"Proteomic and transcriptomic analyses, clinical specimen validation, LAM332 neutralization, CTC clustering assays, apoptosis assays, in vivo mouse metastasis models\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined ligand-receptor interaction with functional in vivo validation across multiple assays, single lab\",\n      \"pmids\": [\"41881953\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"H. pylori infection induces p-STAT3 activation, which transcriptionally upregulates ITGA3; elevated ITGA3 then activates the NF-κB/mTOR signaling axis and enhances TGF-β-related signaling, promoting gastric cancer cell proliferation, EMT, and migration.\",\n      \"method\": \"H. pylori infection of GC cells, p-STAT3 pathway analysis, ITGA3 expression assays, NF-κB/mTOR and TGF-β pathway Western blots, functional proliferation/migration/EMT assays, in vivo tumor growth\",\n      \"journal\": \"Molecular and cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic pathway defined with transcriptional regulation and downstream signaling, in vitro and in vivo, single lab\",\n      \"pmids\": [\"42240927\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ITGA3 is an integrin alpha subunit that forms a heterodimer (α3β1) acting as a cell-surface adhesion and signaling receptor for extracellular matrix ligands including laminin-332 and collagen I; ligand engagement activates FAK/PI3K/AKT/mTOR, ERK, and Src downstream cascades to regulate cell migration, invasion, EMT, anoikis resistance, glycolysis, and progenitor cell self-renewal, while ITGA3 also engages binding partners including VASP, MET, and Siglec-10, is transcriptionally regulated by YY1 and STAT3, post-transcriptionally controlled by multiple miRNAs (miR-223, miR-199 family, miR-101, miR-124/124-3p, miR-183, miR-524-5p, miR-144-5p), and has mRNA stability modulated via S100A16-MOV10; loss of ITGA3 impairs neural stem cell homeostasis, trophoblast invasion via the ULK1-autophagy axis, and alveolar epithelial progenitor self-renewal via FAK/YAP signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ITGA3 is an integrin alpha subunit, derived by proteolytic cleavage into disulfide-linked heavy and light chains and bearing metal-binding motifs and a transmembrane segment characteristic of the integrin superfamily [#0], that pairs with ITGB1 to form a cell-surface receptor coupling extracellular matrix engagement to migration, invasion, and progenitor cell behavior. As the \\u03b13\\u03b21 heterodimer it binds ECM ligands including autocrine collagen I and fibroblast-derived laminin-332, engagement of which drives FAK/PI3K/AKT/mTOR signaling to upregulate HIF1\\u03b1/c-Myc-dependent glycolysis and to promote proliferation, invasion, and circulating-tumor-cell clustering [#13, #25]. Across cancer types ITGA3 acts upstream of FAK/PI3K/AKT, FAK/Src, and ERK cascades and modulates EMT markers to control motility and anoikis resistance [#6, #7, #8]. It physically partners with VASP to regulate stemness and EMT [#10] and cooperates with the MET receptor tyrosine kinase, promoting MET phosphorylation at Tyr1234/1235 and ERK and PI3K/AKT activation [#14]. ITGA3 expression is transcriptionally controlled by YY1 in trophoblasts [#12] and by STAT3 during H. pylori-driven gastric carcinogenesis [#26], post-transcriptionally repressed by numerous miRNAs (miR-223, the miR-199 family, miR-101, miR-124/124-3p, miR-183, miR-524-5p) [#2, #3, #4, #8, #5], and stabilized at the mRNA level via the S100A16-MOV10 axis [#17]. Beyond cancer, ITGA3 supports tissue progenitor homeostasis: it sustains the hippocampal neural stem cell pool against ROS-driven depletion [#15], drives ULK1-dependent autophagy to enable trophoblast invasion [#16], and maintains alveolar AT2 progenitor self-renewal through FAK/YAP signaling, with NPNT engagement stabilizing YAP1 by restraining LATS1/MOB1 [#18, #20]. Sialylated \\u03b13\\u03b21 also functions as a ligand for the macrophage inhibitory checkpoint Siglec-10 to suppress phagocytosis [#22].\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Established the molecular identity of ITGA3 as an integrin alpha subunit, defining the structural basis for its receptor function.\",\n      \"evidence\": \"cDNA cloning, protein purification, and partial amino acid sequencing\",\n      \"pmids\": [\"1691184\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the ligand specificity or signaling output of the protein\", \"Heterodimer partner not functionally characterized in this study\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showed ITGA3 can act non-cell-autonomously, addressing whether the integrin contributes to tumor microenvironment remodeling beyond the cell expressing it.\",\n      \"evidence\": \"Exosome isolation, transwell assays, and ITGA3 inhibition in prostate cancer/prEC cells\",\n      \"pmids\": [\"24371517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism by which exosomal ITGA3 acts on recipient cells unresolved\", \"Whether intact \\u03b13\\u03b21 or cleaved fragments mediate the effect not addressed\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed ITGA3 within post-transcriptional regulatory circuits controlling motility, beginning the mapping of upstream miRNA control.\",\n      \"evidence\": \"miR-223 restoration and ITGA3/ITGB1 siRNA knockdown with migration/invasion assays in prostate cancer\",\n      \"pmids\": [\"26509963\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding inferred from expression rather than reporter assay\", \"Downstream signaling not characterized here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extended ITGA3 as a convergent miRNA target across head/neck, nasopharyngeal cancers and the developing cochlea, linking its dosage to proliferation and metastatic phenotypes.\",\n      \"evidence\": \"Ectopic miRNA expression, ITGA3 rescue, in vivo CAM metastasis model, and conditional Dicer knockout\",\n      \"pmids\": [\"28612520\", \"28102841\", \"28777373\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Tissue-specific selectivity among the many ITGA3-targeting miRNAs unresolved\", \"Whether ITGA3 protein level alone is the rate-limiting effector not isolated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined the downstream signaling consequences of ITGA3, placing it upstream of FAK/AKT/ERK and as a regulator of anoikis sensitivity.\",\n      \"evidence\": \"Luciferase reporter validation of miR-124-3p, siRNA knockdown, phospho-FAK/AKT/ERK Western blots, in vivo anoikis/metastasis assays in PDAC and colorectal cancer\",\n      \"pmids\": [\"29988949\", \"29758195\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The ECM ligand triggering these cascades not identified in these studies\", \"Contribution of ITGB1 partner versus ITGA3 alone not separated\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected ITGA3 to EMT-driving FAK/PI3K/AKT and FAK/Src pathways and to autophagy regulation, broadening its signaling repertoire.\",\n      \"evidence\": \"Luciferase reporter assays, knockdown, EMT marker and pathway Western blots in bladder and papillary thyroid cancer\",\n      \"pmids\": [\"30614803\", \"30941771\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between ITGA3 and autophagy machinery not defined at this stage\", \"Direct versus indirect EMT regulation unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified the first direct physical partner beyond the integrin beta chain, VASP, tying ITGA3 to cytoskeletal regulation of stemness.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, immunofluorescence, sphere formation and migration assays in breast cancer\",\n      \"pmids\": [\"31987909\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis and stoichiometry of the ITGA3-VASP interaction unknown\", \"Whether VASP binding is ligand-engagement dependent not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Implicated ITGA3 in viral biology, indicating a role at the membrane in HIV-1 production in macrophages.\",\n      \"evidence\": \"Gene expression profiling, siRNA knockdown, and viral replication assays in macrophages\",\n      \"pmids\": [\"34242748\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism at viral budding/release stage inferred but not directly demonstrated\", \"Whether ITGA3 acts as adhesion receptor or scaffold in this context unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established direct transcriptional control of ITGA3 by YY1 and linked the axis to FAK phosphorylation and cytoskeletal remodeling in trophoblast invasion.\",\n      \"evidence\": \"ChIP-seq, ChIP, dual-luciferase reporter, gene silencing, and immunofluorescence in trophoblastic cells\",\n      \"pmids\": [\"35970081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether YY1 regulation operates outside trophoblasts not addressed\", \"Upstream signals controlling YY1 in this context unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified physiological ECM ligands and a receptor-tyrosine-kinase co-receptor, converting ITGA3 from an inferred adhesion molecule into a defined signaling receptor for collagen I and a MET partner driving glycolysis and proliferation.\",\n      \"evidence\": \"ITGA3 blocking antibody, Col1 siRNA, MET phospho-Western blots, glycolysis assays, co-IP, and xenografts in PDAC and papillary thyroid cancer\",\n      \"pmids\": [\"39690180\", \"40138447\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether collagen I binds \\u03b13\\u03b21 directly or requires accessory factors not fully resolved\", \"Structural interface of ITGA3-MET cooperation unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated a tissue-protective progenitor-maintenance role for ITGA3 in neural and alveolar stem cells through ROS-sensitive FAK/YAP signaling and an autophagy/ULK1 axis in trophoblasts.\",\n      \"evidence\": \"Conditional Itga3 overexpression/knockdown, ICH and CS-exposed mouse models, alveolar organoids, RNA-seq, ULK1 assays, NAC intervention\",\n      \"pmids\": [\"38367510\", \"39437445\", \"41270956\", \"38755258\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How ROS suppresses ITGA3 expression mechanistically unresolved\", \"Whether ECM ligand engagement is required for progenitor maintenance not isolated\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed ITGA3 mRNA stability control by the S100A16-MOV10 axis, adding a post-transcriptional input distinct from miRNA repression.\",\n      \"evidence\": \"Co-IP (S100A16-MOV10), RNA immunoprecipitation (MOV10-ITGA3 mRNA), and actinomycin D stability assay in lung adenocarcinoma\",\n      \"pmids\": [\"39450567\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Sequence elements in ITGA3 mRNA bound by MOV10 not mapped\", \"Generality across tissues unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Positioned ITGA3 in immune evasion and additional ECM/transcriptional circuits, identifying it as a Siglec-10 glyco-ligand, a SOX10-IRF1 effector, and a STAT3 target, and detailing NPNT-mediated YAP1 stabilization.\",\n      \"evidence\": \"Ligand identification, monoclonal antibody blockade, phagocytosis assays, genetic epistasis, FAK inhibitor and Escin treatments, NPNT mouse models, laminin-332 neutralization across PDAC, melanoma, gastric cancer and fibrosis\",\n      \"pmids\": [\"40444575\", \"40808260\", \"41881953\", \"42240927\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Sialylation enzymes generating the Siglec-10 epitope on \\u03b13\\u03b21 not defined\", \"Interplay between the many parallel ITGA3 axes within a single cell unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the diverse ligand engagements, partner interactions, and transcriptional/post-transcriptional inputs are integrated into context-specific ITGA3 outputs, and the structural basis of its non-canonical partnerships, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of ITGA3 ligand or co-receptor interfaces in the corpus\", \"No causative human Mendelian disease mutation documented in the timeline\", \"Quantitative hierarchy among competing regulatory inputs unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [13, 25, 0]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [13, 14, 25]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [22]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 13, 22]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [6, 8, 13, 14]},\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [13, 25]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [15, 18, 16]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [22, 11]}\n    ],\n    \"complexes\": [\"integrin alpha3beta1\"],\n    \"partners\": [\"ITGB1\", \"VASP\", \"MET\", \"NPNT\", \"MOV10\", \"SIGLEC10\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}