{"gene":"ITGA11","run_date":"2026-04-28T18:06:54","timeline":{"discoveries":[{"year":1999,"finding":"Human ITGA11 encodes an integrin alpha-11 subunit with a large extracellular domain containing a 207-residue I-domain, a transmembrane domain, and a short 24-amino acid cytoplasmic domain with an incompletely preserved GFFKR motif; it is structurally similar to collagen-binding integrin alpha-subunits and its gene localizes to chromosome 15q22.3-q23.","method":"cDNA cloning, sequence analysis, chromosomal localization by FISH/mapping","journal":"Genomics","confidence":"High","confidence_rationale":"Tier 1 — original cloning and structural characterization with multiple methods","pmids":["10486209"],"is_preprint":false},{"year":2002,"finding":"The ITGA11 gene spans 30 exons; a major transcription start site was mapped 30 nucleotides upstream of the translation start. Promoter dissection in HT1080 fibrosarcoma cells identified a core promoter (nt -127 to +25), a silencer region (nt -400 to -127), and an enhancer region (nt -1519 to -400) driving alpha11 transcription in mesenchymal cells.","method":"Genomic PCR, oligo-capping, luciferase reporter constructs in HT1080 cells","journal":"Matrix biology","confidence":"High","confidence_rationale":"Tier 1 — functional promoter dissection with reporter assays and transcription start site mapping","pmids":["12392762"],"is_preprint":false},{"year":2010,"finding":"Progesterone upregulates ITGA11 expression and phosphorylated focal adhesion kinase (pFAK) in rat cervical stromal cells, while mifepristone (progesterone antagonist) blocks these effects in vitro; ERK1/2 signaling pathway mediates mifepristone-induced upregulation of the related collagen-binding integrin ITGA2.","method":"Western blot on primary rat cervical stromal cells, in vivo gestational tissue harvest, pharmacological inhibition of ERK1/2","journal":"Reproductive sciences","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD/OE equivalent via pharmacological manipulation with defined signaling readout, single lab","pmids":["20959644"],"is_preprint":false},{"year":2015,"finding":"FGF2 downregulates ITGA11 expression and removes it from focal adhesions in human dermal fibroblasts via ERK1/2 activity, overriding TGFβ1-mediated induction of ITGA11; TGFβ1 cannot rescue ITGA11 expression in the presence of FGF2.","method":"RT-PCR, qRT-PCR, Western blotting, immunocytochemistry, ERK1/2 inhibition","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods, defined signaling pathway, single lab","pmids":["26403263"],"is_preprint":false},{"year":2015,"finding":"miR-126a-3p directly binds to the 3' UTR of Itga11 mRNA to inhibit its translation and reduce mRNA stability; in vivo loss of miR-126a-3p significantly reduced the number of embryo implantation sites, positioning Itga11 as a downstream effector of miR-126a-3p in endometrial cell migration and invasion during implantation.","method":"Luciferase reporter assay, Transwell migration/invasion assay, in vivo miR-126a-3p inhibition in mice","journal":"Reproductive biomedicine online","confidence":"Medium","confidence_rationale":"Tier 2 — luciferase validation of miRNA-target interaction plus in vivo functional readout","pmids":["26194885"],"is_preprint":false},{"year":2020,"finding":"FEZF1-AS1 lncRNA acts as a competing endogenous RNA (ceRNA) sponging miR-516b-5p to upregulate ITGA11 in NSCLC cells; miR-516b-5p directly targets ITGA11 (validated by luciferase reporter), and loss of FEZF1-AS1 decreases ITGA11 expression, reducing cell proliferation and migration.","method":"RNA-binding protein immunoprecipitation, RNA pulldown, luciferase reporter assay, loss-of-function assays","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods confirming ceRNA mechanism, single lab","pmids":["33174014"],"is_preprint":false},{"year":2021,"finding":"CircRNA_100290 acts as a sponge for miR-29b-3p, which directly targets ITGA11; knockdown of circRNA_100290 reduces ITGA11 expression and inhibits gastric cancer cell proliferation, migration, invasion, and EMT, establishing a circRNA_100290/miR-29b-3p/ITGA11 regulatory axis.","method":"Dual-luciferase reporter assay, RNA immunoprecipitation, Western blot, siRNA knockdown","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 — luciferase and RIP validation of axis, functional cellular readouts, single lab","pmids":["34182990"],"is_preprint":false},{"year":2022,"finding":"CircPDSS1 directly binds miR-515-5p to sequester it from ITGA11 mRNA, thereby promoting ITGA11 expression and conferring cisplatin resistance in gastric cancer; miR-515-5p overexpression improves cisplatin sensitivity by downregulating ITGA11, validated in vivo in a xenograft model.","method":"Dual-luciferase reporter assay, RNA immunoprecipitation, Western blot, xenograft mouse model","journal":"Journal of chemotherapy","confidence":"Medium","confidence_rationale":"Tier 2 — multiple methods validating ceRNA axis plus in vivo confirmation, single lab","pmids":["36484486"],"is_preprint":false},{"year":2023,"finding":"Genetic deletion of Itga11 in mice (Itga11-/- ) substantially reduces psoriasiform dermatitis severity (clinical, histopathological, and molecular phenotypes) induced by imiquimod, with reduced fibroblasts and inflammatory cells (macrophages, T cells, tissue-resident memory T cells) and altered transcriptomes enriched in ECM organization, immune, and lipid metabolism pathways.","method":"Forward genetics screen across 13 inbred mouse strains, Itga11-/- knockout mice, skin transcriptomics, immunohistochemistry","journal":"The Journal of pathology","confidence":"High","confidence_rationale":"Tier 2 — genetic KO with defined cellular and molecular phenotype, forward genetics corroboration","pmids":["37565309"],"is_preprint":false},{"year":2024,"finding":"PDGFRα+ITGA11+ CAFs promote lymphangiogenesis by ITGA11 acting as a surface receptor that directly recognizes SELE (E-selectin) on lymphatic endothelial cells, activating the SRC–pVEGFR3–MAPK signaling pathway; additionally, CHI3L1 secreted by these CAFs remodels surrounding matrix to facilitate cancer cell intravasation.","method":"Single-cell RNA sequencing, spatial transcriptomics, PDGFRα+ITGA11+ CAF-specific deficient mouse model, 910-case clinical cohort","journal":"Cancer cell","confidence":"High","confidence_rationale":"Tier 2 — cell-type-specific KO mouse model plus multi-omics and large clinical validation; ITGA11-SELE interaction with downstream pathway activation","pmids":["38428409"],"is_preprint":false},{"year":2024,"finding":"Itga11 overexpression in rat bone marrow mesenchymal stem cells (rBMSCs) under hypoxia inhibits proliferation and angiogenesis while enhancing osteogenic differentiation; knockdown has the opposite effect. These effects are mediated through activation of the PI3K/Akt signaling pathway.","method":"siRNA knockdown, pcDNA overexpression, CCK-8 assay, tube formation assay, alizarin red staining, Western blot","journal":"Tissue & cell","confidence":"Medium","confidence_rationale":"Tier 2 — gain- and loss-of-function with multiple cellular readouts and signaling pathway validation, single lab","pmids":["39566247"],"is_preprint":false},{"year":2025,"finding":"LIPUS upregulates ITGA11 in rat BMSCs to promote osteogenic differentiation and implant osseointegration by increasing activity of the FAK/PI3K/AKT/GSK3β/β-catenin focal adhesion pathway.","method":"Micro-CT, Western blot, RT-PCR, ALP staining, alizarin red staining, bioinformatics (random forest, KEGG), in vivo rat femur implant model","journal":"BMC oral health","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo implant model plus in vitro signaling pathway validation, single lab","pmids":["39755586"],"is_preprint":false},{"year":2026,"finding":"ITGA11 promotes myoblast differentiation via the FAK/Paxillin-Akt-GSK3β pathway; dexamethasone-induced stress suppresses this cascade through glucocorticoid receptor (GR)-mediated transcriptome remodeling, and overexpression of ITGA11 rescues Dex-induced suppression of differentiation.","method":"Transcriptomic analysis, overexpression/siRNA interference, Western blot, GR antagonist (RU486), sheep fetal myoblasts","journal":"Journal of agricultural and food chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — gain- and loss-of-function with defined signaling pathway and pharmacological validation, single lab","pmids":["41720752"],"is_preprint":false},{"year":2024,"finding":"NSD2 transcriptionally upregulates Itga11 (and Itga4) to activate the FAK/AKT pathway, promoting renal cell carcinoma tumorigenesis and cell proliferation on stiff matrix; FAK inhibition reverses NSD2-driven phenotypes in vivo.","method":"Kidney-specific MYC/NSD2 overexpression mouse model, FAK inhibition in vivo and in vitro, PEGDA hydrogel stiffness assay","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 — preprint, transcriptional upregulation of Itga11 by NSD2 shown but direct mechanism of ITGA11 action not individually dissected","pmids":["bio_10.1101_2024.10.21.619559"],"is_preprint":true}],"current_model":"ITGA11 encodes an integrin alpha-11 subunit that forms the alpha11beta1 collagen-binding heterodimer, is regulated transcriptionally by a defined promoter and post-transcriptionally by multiple ceRNA/miRNA axes (miR-516b-5p, miR-29b-3p, miR-515-5p, miR-126a-3p), and signals through FAK/PI3K/AKT and SRC/VEGFR3/MAPK pathways to drive fibroblast-mediated ECM remodeling, lymphangiogenesis (via direct binding to SELE on lymphatic endothelial cells), osteogenic differentiation, myogenesis, and skin inflammation, with its expression regulated by progesterone (upregulating) and FGF2/ERK1/2 (downregulating) in a context-dependent manner."},"narrative":{"teleology":[{"year":1999,"claim":"Cloning of ITGA11 established it as a new collagen-receptor integrin alpha subunit, resolving its domain architecture (I-domain, transmembrane, short cytoplasmic tail with variant GFFKR motif) and chromosomal location (15q22.3-q23).","evidence":"cDNA cloning, sequence analysis, and FISH/mapping in human cells","pmids":["10486209"],"confidence":"High","gaps":["No ligand-binding specificity data at this stage","Beta-subunit pairing not experimentally confirmed here","No functional assays performed"]},{"year":2002,"claim":"Promoter dissection revealed a modular transcriptional architecture (core promoter, silencer, enhancer) governing ITGA11 expression in mesenchymal cells, explaining its tissue-restricted expression pattern.","evidence":"Luciferase reporter constructs and oligo-capping in HT1080 fibrosarcoma cells","pmids":["12392762"],"confidence":"High","gaps":["Trans-acting transcription factors binding these elements not identified","Regulation in non-mesenchymal contexts not tested"]},{"year":2010,"claim":"Hormonal regulation of ITGA11 was demonstrated: progesterone upregulates ITGA11 and pFAK in cervical stromal cells, linking integrin alpha-11 to reproductive tissue remodeling.","evidence":"Western blot on primary rat cervical stromal cells with progesterone/mifepristone treatment","pmids":["20959644"],"confidence":"Medium","gaps":["Mechanism of progesterone-mediated transcriptional or post-transcriptional upregulation not defined","Not confirmed in human tissue"]},{"year":2015,"claim":"Two independent regulatory inputs were resolved: FGF2/ERK1/2 signaling dominantly suppresses ITGA11 even in the presence of TGFβ1 in dermal fibroblasts, while miR-126a-3p directly targets the ITGA11 3′ UTR to control endometrial cell migration during embryo implantation.","evidence":"RT-PCR, Western blot, ERK1/2 inhibition in fibroblasts; luciferase reporter and in vivo miR-126a-3p inhibition in mice","pmids":["26403263","26194885"],"confidence":"Medium","gaps":["Whether FGF2 acts at the ITGA11 promoter or post-transcriptionally not resolved","In vivo implantation phenotype not rescued by ITGA11 re-expression"]},{"year":2020,"claim":"A ceRNA regulatory paradigm was established: multiple non-coding RNAs (FEZF1-AS1/miR-516b-5p, circRNA_100290/miR-29b-3p, circPDSS1/miR-515-5p) converge on ITGA11 to modulate its expression in cancer contexts, controlling proliferation, migration, EMT, and chemoresistance.","evidence":"Dual-luciferase reporter, RNA immunoprecipitation, knockdown/overexpression, and xenograft models in NSCLC and gastric cancer cells","pmids":["33174014","34182990","36484486"],"confidence":"Medium","gaps":["Functional contribution of ITGA11 itself versus other miRNA targets not individually dissected","ceRNA axes not validated across independent labs","Endogenous stoichiometry of ceRNA competition not assessed"]},{"year":2023,"claim":"Genetic loss-of-function in Itga11-knockout mice demonstrated a non-redundant role in skin inflammation, with Itga11 deletion substantially reducing psoriasiform dermatitis severity, fibroblast numbers, and immune cell infiltration.","evidence":"Itga11−/− knockout mice with imiquimod-induced psoriasis, skin transcriptomics, immunohistochemistry, forward genetics across 13 inbred strains","pmids":["37565309"],"confidence":"High","gaps":["Whether the phenotype is fibroblast-intrinsic or involves immune cell-expressed ITGA11 not resolved","Downstream signaling pathway mediating immune recruitment not defined"]},{"year":2024,"claim":"ITGA11 on PDGFRα+ cancer-associated fibroblasts was shown to directly bind E-selectin (SELE) on lymphatic endothelial cells, activating SRC–pVEGFR3–MAPK signaling to drive lymphangiogenesis and facilitate cancer cell intravasation — establishing a cell-cell adhesion function beyond classical collagen binding.","evidence":"Single-cell RNA-seq, spatial transcriptomics, PDGFRα+ITGA11+ CAF-specific deficient mouse model, 910-case clinical cohort","pmids":["38428409"],"confidence":"High","gaps":["Structural basis of ITGA11–SELE interaction not determined","Whether beta-1 subunit is required for SELE binding not tested"]},{"year":2024,"claim":"ITGA11 was positioned as a key effector of the FAK/PI3K/AKT pathway in osteogenic differentiation: overexpression in bone marrow MSCs under hypoxia promoted osteogenesis while inhibiting proliferation and angiogenesis, and LIPUS-mediated ITGA11 upregulation enhanced osseointegration in vivo.","evidence":"Gain- and loss-of-function in rat BMSCs, in vivo rat femur implant model with micro-CT and signaling pathway analysis","pmids":["39566247","39755586"],"confidence":"Medium","gaps":["Direct collagen-binding requirement for osteogenic signaling not tested","Pathway specificity relative to other integrins not established"]},{"year":2026,"claim":"ITGA11 was shown to promote myoblast differentiation through FAK/Paxillin–Akt–GSK3β signaling, and glucocorticoid receptor-mediated transcriptional suppression of ITGA11 was identified as the mechanism of dexamethasone-induced differentiation arrest.","evidence":"Overexpression/siRNA, Western blot, GR antagonist RU486, sheep fetal myoblasts","pmids":["41720752"],"confidence":"Medium","gaps":["Whether GR directly binds the ITGA11 promoter not demonstrated","Applicability to human myogenesis not tested"]},{"year":null,"claim":"The structural basis of ITGA11's dual ligand recognition (collagen I and E-selectin), the identity of transcription factors acting on its promoter elements, and the fibroblast-intrinsic versus immune cell-mediated contributions to its inflammatory phenotype remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No crystal structure of ITGA11 I-domain with collagen or SELE","Trans-acting factors for the defined promoter silencer/enhancer unknown","Conditional cell-type-specific knockouts in inflammation not reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[0,9]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[9]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,3,9]},{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[8,9]}],"pathway":[{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[8,9]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,9,10,11,12]},{"term_id":"R-HSA-1500931","term_label":"Cell-Cell communication","supporting_discovery_ids":[9]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[8]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[10,11,12]}],"complexes":["alpha11beta1 integrin"],"partners":["ITGB1","SELE","FAK","PDGFRA"],"other_free_text":[]},"mechanistic_narrative":"ITGA11 encodes integrin alpha-11, a collagen-binding integrin alpha subunit that heterodimerizes with beta-1 to mediate cell-matrix and cell-cell adhesion, fibroblast-driven extracellular matrix remodeling, and downstream intracellular signaling through the FAK/PI3K/AKT and SRC/MAPK pathways. The alpha-11 subunit contains a 207-residue I-domain critical for collagen recognition, a transmembrane segment, and a short cytoplasmic tail with a variant GFFKR motif, and its transcription in mesenchymal cells is driven by a defined core promoter with distinct silencer and enhancer elements [PMID:10486209, PMID:12392762]. ITGA11 expression is post-transcriptionally regulated by multiple miRNA–ceRNA axes (miR-516b-5p, miR-29b-3p, miR-515-5p, miR-126a-3p), and at the signaling level it activates FAK/Paxillin–AKT–GSK3β to promote osteogenic and myogenic differentiation, while on cancer-associated fibroblasts it directly engages E-selectin (SELE) on lymphatic endothelial cells to activate SRC–pVEGFR3–MAPK-dependent lymphangiogenesis [PMID:33174014, PMID:38428409, PMID:39755586, PMID:41720752]. Genetic deletion of Itga11 in mice markedly attenuates psoriasiform skin inflammation by reducing fibroblast and immune cell infiltration and altering ECM-organization and immune transcriptional programs [PMID:37565309]."},"prefetch_data":{"uniprot":{"accession":"Q9UKX5","full_name":"Integrin alpha-11","aliases":[],"length_aa":1188,"mass_kda":133.5,"function":"Integrin alpha-11/beta-1 is a receptor for collagen","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q9UKX5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ITGA11","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ITGA11","total_profiled":1310},"omim":[{"mim_id":"612632","title":"USHER SYNDROME, TYPE IH; USH1H","url":"https://www.omim.org/entry/612632"},{"mim_id":"604789","title":"INTEGRIN, ALPHA-11; ITGA11","url":"https://www.omim.org/entry/604789"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"blood vessel","ntpm":74.1},{"tissue":"endometrium 1","ntpm":28.8}],"url":"https://www.proteinatlas.org/search/ITGA11"},"hgnc":{"alias_symbol":["HsT18964"],"prev_symbol":[]},"alphafold":{"accession":"Q9UKX5","domains":[{"cath_id":"3.40.50.410","chopping":"164-217_226-233_246-355","consensus_level":"high","plddt":89.9334,"start":164,"end":355},{"cath_id":"2.60.40.1460","chopping":"639-776","consensus_level":"high","plddt":85.8318,"start":639,"end":776},{"cath_id":"2.60.40.1510","chopping":"792-954","consensus_level":"high","plddt":86.4497,"start":792,"end":954},{"cath_id":"2.60.40.1530","chopping":"958-1134","consensus_level":"high","plddt":83.909,"start":958,"end":1134},{"cath_id":"2.40.128","chopping":"29-154","consensus_level":"medium","plddt":90.7382,"start":29,"end":154}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UKX5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UKX5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UKX5-F1-predicted_aligned_error_v6.png","plddt_mean":85.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ITGA11","jax_strain_url":"https://www.jax.org/strain/search?query=ITGA11"},"sequence":{"accession":"Q9UKX5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UKX5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UKX5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UKX5"}},"corpus_meta":[{"pmid":"38428409","id":"PMC_38428409","title":"PDGFRα+ITGA11+ fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay.","date":"2024","source":"Cancer cell","url":"https://pubmed.ncbi.nlm.nih.gov/38428409","citation_count":113,"is_preprint":false},{"pmid":"17016581","id":"PMC_17016581","title":"Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer.","date":"2006","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/17016581","citation_count":89,"is_preprint":false},{"pmid":"33174014","id":"PMC_33174014","title":"Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis.","date":"2020","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33174014","citation_count":41,"is_preprint":false},{"pmid":"34182990","id":"PMC_34182990","title":"CircRNA_100290 promotes GC cell proliferation and invasion via the miR-29b-3p/ITGA11 axis and is regulated by EIF4A3.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/34182990","citation_count":36,"is_preprint":false},{"pmid":"10486209","id":"PMC_10486209","title":"Cloning, sequence analysis, and chromosomal localization of the novel human integrin alpha11 subunit (ITGA11).","date":"1999","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10486209","citation_count":27,"is_preprint":false},{"pmid":"26194885","id":"PMC_26194885","title":"Mmu-miR-126a-3p plays a role in murine embryo implantation by regulating Itga11.","date":"2015","source":"Reproductive biomedicine online","url":"https://pubmed.ncbi.nlm.nih.gov/26194885","citation_count":25,"is_preprint":false},{"pmid":"20959644","id":"PMC_20959644","title":"Progesterone modulates integrin {alpha}2 (ITGA2) and {alpha}11 (ITGA11) in the pregnant cervix.","date":"2010","source":"Reproductive sciences (Thousand Oaks, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/20959644","citation_count":19,"is_preprint":false},{"pmid":"12392762","id":"PMC_12392762","title":"Analysis of the human integrin alpha11 gene (ITGA11) and its promoter.","date":"2002","source":"Matrix biology : journal of the International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/12392762","citation_count":18,"is_preprint":false},{"pmid":"26403263","id":"PMC_26403263","title":"FGF2 Overrides TGFβ1-Driven Integrin ITGA11 Expression in Human Dermal Fibroblasts.","date":"2015","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26403263","citation_count":18,"is_preprint":false},{"pmid":"36484486","id":"PMC_36484486","title":"Depletion of circPDSS1 inhibits ITGA11 production to confer cisplatin sensitivity through miR-515-5p in gastric cancer.","date":"2022","source":"Journal of chemotherapy (Florence, Italy)","url":"https://pubmed.ncbi.nlm.nih.gov/36484486","citation_count":7,"is_preprint":false},{"pmid":"37565309","id":"PMC_37565309","title":"Forward genetics and functional analysis highlight Itga11 as a modulator of murine psoriasiform dermatitis.","date":"2023","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/37565309","citation_count":5,"is_preprint":false},{"pmid":"39791208","id":"PMC_39791208","title":"NGR1 reduces neuronal apoptosis through regulation of ITGA11 following subarachnoid hemorrhage.","date":"2025","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/39791208","citation_count":2,"is_preprint":false},{"pmid":"39755586","id":"PMC_39755586","title":"LIPUS promotes osteogenic differentiation of rat BMSCs and osseointegration of dental implants by regulating ITGA11 and focal adhesion pathway.","date":"2025","source":"BMC oral health","url":"https://pubmed.ncbi.nlm.nih.gov/39755586","citation_count":1,"is_preprint":false},{"pmid":"39566247","id":"PMC_39566247","title":"Itga11 promotes osteogenic differentiation, inhibits angiogenesis and proliferation of mesenchymal stem cells under hypoxia.","date":"2024","source":"Tissue & cell","url":"https://pubmed.ncbi.nlm.nih.gov/39566247","citation_count":0,"is_preprint":false},{"pmid":"41722833","id":"PMC_41722833","title":"Aflatoxin B1 accelerates diabetic nephropathy progression via ITGA11/LTBP1-dependent oxidative and fibrotic pathways: Evidence from multi-omics and molecular simulations.","date":"2026","source":"Chemico-biological interactions","url":"https://pubmed.ncbi.nlm.nih.gov/41722833","citation_count":0,"is_preprint":false},{"pmid":"41720752","id":"PMC_41720752","title":"Stress Inhibits Myogenic Differentiation via Transcriptome Remodeling and GR-Mediated Suppression of the ITGA11-FAK/Paxillin-Akt-GSK3β Cascade.","date":"2026","source":"Journal of 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signaling","date":"2024-10-24","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.21.619559","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12291,"output_tokens":3373,"usd":0.043734},"stage2":{"model":"claude-opus-4-6","input_tokens":6785,"output_tokens":2764,"usd":0.154537},"total_usd":0.198271,"stage1_batch_id":"msgbatch_01DzrsgVgYngY1hvM3DU1yF2","stage2_batch_id":"msgbatch_01KA9b7iRzKFdhoBUT7vCvSe","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"Human ITGA11 encodes an integrin alpha-11 subunit with a large extracellular domain containing a 207-residue I-domain, a transmembrane domain, and a short 24-amino acid cytoplasmic domain with an incompletely preserved GFFKR motif; it is structurally similar to collagen-binding integrin alpha-subunits and its gene localizes to chromosome 15q22.3-q23.\",\n      \"method\": \"cDNA cloning, sequence analysis, chromosomal localization by FISH/mapping\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — original cloning and structural characterization with multiple methods\",\n      \"pmids\": [\"10486209\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The ITGA11 gene spans 30 exons; a major transcription start site was mapped 30 nucleotides upstream of the translation start. Promoter dissection in HT1080 fibrosarcoma cells identified a core promoter (nt -127 to +25), a silencer region (nt -400 to -127), and an enhancer region (nt -1519 to -400) driving alpha11 transcription in mesenchymal cells.\",\n      \"method\": \"Genomic PCR, oligo-capping, luciferase reporter constructs in HT1080 cells\",\n      \"journal\": \"Matrix biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — functional promoter dissection with reporter assays and transcription start site mapping\",\n      \"pmids\": [\"12392762\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Progesterone upregulates ITGA11 expression and phosphorylated focal adhesion kinase (pFAK) in rat cervical stromal cells, while mifepristone (progesterone antagonist) blocks these effects in vitro; ERK1/2 signaling pathway mediates mifepristone-induced upregulation of the related collagen-binding integrin ITGA2.\",\n      \"method\": \"Western blot on primary rat cervical stromal cells, in vivo gestational tissue harvest, pharmacological inhibition of ERK1/2\",\n      \"journal\": \"Reproductive sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD/OE equivalent via pharmacological manipulation with defined signaling readout, single lab\",\n      \"pmids\": [\"20959644\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"FGF2 downregulates ITGA11 expression and removes it from focal adhesions in human dermal fibroblasts via ERK1/2 activity, overriding TGFβ1-mediated induction of ITGA11; TGFβ1 cannot rescue ITGA11 expression in the presence of FGF2.\",\n      \"method\": \"RT-PCR, qRT-PCR, Western blotting, immunocytochemistry, ERK1/2 inhibition\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods, defined signaling pathway, single lab\",\n      \"pmids\": [\"26403263\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"miR-126a-3p directly binds to the 3' UTR of Itga11 mRNA to inhibit its translation and reduce mRNA stability; in vivo loss of miR-126a-3p significantly reduced the number of embryo implantation sites, positioning Itga11 as a downstream effector of miR-126a-3p in endometrial cell migration and invasion during implantation.\",\n      \"method\": \"Luciferase reporter assay, Transwell migration/invasion assay, in vivo miR-126a-3p inhibition in mice\",\n      \"journal\": \"Reproductive biomedicine online\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — luciferase validation of miRNA-target interaction plus in vivo functional readout\",\n      \"pmids\": [\"26194885\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"FEZF1-AS1 lncRNA acts as a competing endogenous RNA (ceRNA) sponging miR-516b-5p to upregulate ITGA11 in NSCLC cells; miR-516b-5p directly targets ITGA11 (validated by luciferase reporter), and loss of FEZF1-AS1 decreases ITGA11 expression, reducing cell proliferation and migration.\",\n      \"method\": \"RNA-binding protein immunoprecipitation, RNA pulldown, luciferase reporter assay, loss-of-function assays\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods confirming ceRNA mechanism, single lab\",\n      \"pmids\": [\"33174014\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CircRNA_100290 acts as a sponge for miR-29b-3p, which directly targets ITGA11; knockdown of circRNA_100290 reduces ITGA11 expression and inhibits gastric cancer cell proliferation, migration, invasion, and EMT, establishing a circRNA_100290/miR-29b-3p/ITGA11 regulatory axis.\",\n      \"method\": \"Dual-luciferase reporter assay, RNA immunoprecipitation, Western blot, siRNA knockdown\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — luciferase and RIP validation of axis, functional cellular readouts, single lab\",\n      \"pmids\": [\"34182990\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CircPDSS1 directly binds miR-515-5p to sequester it from ITGA11 mRNA, thereby promoting ITGA11 expression and conferring cisplatin resistance in gastric cancer; miR-515-5p overexpression improves cisplatin sensitivity by downregulating ITGA11, validated in vivo in a xenograft model.\",\n      \"method\": \"Dual-luciferase reporter assay, RNA immunoprecipitation, Western blot, xenograft mouse model\",\n      \"journal\": \"Journal of chemotherapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods validating ceRNA axis plus in vivo confirmation, single lab\",\n      \"pmids\": [\"36484486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Genetic deletion of Itga11 in mice (Itga11-/- ) substantially reduces psoriasiform dermatitis severity (clinical, histopathological, and molecular phenotypes) induced by imiquimod, with reduced fibroblasts and inflammatory cells (macrophages, T cells, tissue-resident memory T cells) and altered transcriptomes enriched in ECM organization, immune, and lipid metabolism pathways.\",\n      \"method\": \"Forward genetics screen across 13 inbred mouse strains, Itga11-/- knockout mice, skin transcriptomics, immunohistochemistry\",\n      \"journal\": \"The Journal of pathology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with defined cellular and molecular phenotype, forward genetics corroboration\",\n      \"pmids\": [\"37565309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PDGFRα+ITGA11+ CAFs promote lymphangiogenesis by ITGA11 acting as a surface receptor that directly recognizes SELE (E-selectin) on lymphatic endothelial cells, activating the SRC–pVEGFR3–MAPK signaling pathway; additionally, CHI3L1 secreted by these CAFs remodels surrounding matrix to facilitate cancer cell intravasation.\",\n      \"method\": \"Single-cell RNA sequencing, spatial transcriptomics, PDGFRα+ITGA11+ CAF-specific deficient mouse model, 910-case clinical cohort\",\n      \"journal\": \"Cancer cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — cell-type-specific KO mouse model plus multi-omics and large clinical validation; ITGA11-SELE interaction with downstream pathway activation\",\n      \"pmids\": [\"38428409\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Itga11 overexpression in rat bone marrow mesenchymal stem cells (rBMSCs) under hypoxia inhibits proliferation and angiogenesis while enhancing osteogenic differentiation; knockdown has the opposite effect. These effects are mediated through activation of the PI3K/Akt signaling pathway.\",\n      \"method\": \"siRNA knockdown, pcDNA overexpression, CCK-8 assay, tube formation assay, alizarin red staining, Western blot\",\n      \"journal\": \"Tissue & cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — gain- and loss-of-function with multiple cellular readouts and signaling pathway validation, single lab\",\n      \"pmids\": [\"39566247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"LIPUS upregulates ITGA11 in rat BMSCs to promote osteogenic differentiation and implant osseointegration by increasing activity of the FAK/PI3K/AKT/GSK3β/β-catenin focal adhesion pathway.\",\n      \"method\": \"Micro-CT, Western blot, RT-PCR, ALP staining, alizarin red staining, bioinformatics (random forest, KEGG), in vivo rat femur implant model\",\n      \"journal\": \"BMC oral health\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo implant model plus in vitro signaling pathway validation, single lab\",\n      \"pmids\": [\"39755586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ITGA11 promotes myoblast differentiation via the FAK/Paxillin-Akt-GSK3β pathway; dexamethasone-induced stress suppresses this cascade through glucocorticoid receptor (GR)-mediated transcriptome remodeling, and overexpression of ITGA11 rescues Dex-induced suppression of differentiation.\",\n      \"method\": \"Transcriptomic analysis, overexpression/siRNA interference, Western blot, GR antagonist (RU486), sheep fetal myoblasts\",\n      \"journal\": \"Journal of agricultural and food chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — gain- and loss-of-function with defined signaling pathway and pharmacological validation, single lab\",\n      \"pmids\": [\"41720752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NSD2 transcriptionally upregulates Itga11 (and Itga4) to activate the FAK/AKT pathway, promoting renal cell carcinoma tumorigenesis and cell proliferation on stiff matrix; FAK inhibition reverses NSD2-driven phenotypes in vivo.\",\n      \"method\": \"Kidney-specific MYC/NSD2 overexpression mouse model, FAK inhibition in vivo and in vitro, PEGDA hydrogel stiffness assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — preprint, transcriptional upregulation of Itga11 by NSD2 shown but direct mechanism of ITGA11 action not individually dissected\",\n      \"pmids\": [\"bio_10.1101_2024.10.21.619559\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"ITGA11 encodes an integrin alpha-11 subunit that forms the alpha11beta1 collagen-binding heterodimer, is regulated transcriptionally by a defined promoter and post-transcriptionally by multiple ceRNA/miRNA axes (miR-516b-5p, miR-29b-3p, miR-515-5p, miR-126a-3p), and signals through FAK/PI3K/AKT and SRC/VEGFR3/MAPK pathways to drive fibroblast-mediated ECM remodeling, lymphangiogenesis (via direct binding to SELE on lymphatic endothelial cells), osteogenic differentiation, myogenesis, and skin inflammation, with its expression regulated by progesterone (upregulating) and FGF2/ERK1/2 (downregulating) in a context-dependent manner.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ITGA11 encodes integrin alpha-11, a collagen-binding integrin alpha subunit that heterodimerizes with beta-1 to mediate cell-matrix and cell-cell adhesion, fibroblast-driven extracellular matrix remodeling, and downstream intracellular signaling through the FAK/PI3K/AKT and SRC/MAPK pathways. The alpha-11 subunit contains a 207-residue I-domain critical for collagen recognition, a transmembrane segment, and a short cytoplasmic tail with a variant GFFKR motif, and its transcription in mesenchymal cells is driven by a defined core promoter with distinct silencer and enhancer elements [PMID:10486209, PMID:12392762]. ITGA11 expression is post-transcriptionally regulated by multiple miRNA–ceRNA axes (miR-516b-5p, miR-29b-3p, miR-515-5p, miR-126a-3p), and at the signaling level it activates FAK/Paxillin–AKT–GSK3β to promote osteogenic and myogenic differentiation, while on cancer-associated fibroblasts it directly engages E-selectin (SELE) on lymphatic endothelial cells to activate SRC–pVEGFR3–MAPK-dependent lymphangiogenesis [PMID:33174014, PMID:38428409, PMID:39755586, PMID:41720752]. Genetic deletion of Itga11 in mice markedly attenuates psoriasiform skin inflammation by reducing fibroblast and immune cell infiltration and altering ECM-organization and immune transcriptional programs [PMID:37565309].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Cloning of ITGA11 established it as a new collagen-receptor integrin alpha subunit, resolving its domain architecture (I-domain, transmembrane, short cytoplasmic tail with variant GFFKR motif) and chromosomal location (15q22.3-q23).\",\n      \"evidence\": \"cDNA cloning, sequence analysis, and FISH/mapping in human cells\",\n      \"pmids\": [\"10486209\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No ligand-binding specificity data at this stage\", \"Beta-subunit pairing not experimentally confirmed here\", \"No functional assays performed\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Promoter dissection revealed a modular transcriptional architecture (core promoter, silencer, enhancer) governing ITGA11 expression in mesenchymal cells, explaining its tissue-restricted expression pattern.\",\n      \"evidence\": \"Luciferase reporter constructs and oligo-capping in HT1080 fibrosarcoma cells\",\n      \"pmids\": [\"12392762\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trans-acting transcription factors binding these elements not identified\", \"Regulation in non-mesenchymal contexts not tested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Hormonal regulation of ITGA11 was demonstrated: progesterone upregulates ITGA11 and pFAK in cervical stromal cells, linking integrin alpha-11 to reproductive tissue remodeling.\",\n      \"evidence\": \"Western blot on primary rat cervical stromal cells with progesterone/mifepristone treatment\",\n      \"pmids\": [\"20959644\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of progesterone-mediated transcriptional or post-transcriptional upregulation not defined\", \"Not confirmed in human tissue\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Two independent regulatory inputs were resolved: FGF2/ERK1/2 signaling dominantly suppresses ITGA11 even in the presence of TGFβ1 in dermal fibroblasts, while miR-126a-3p directly targets the ITGA11 3′ UTR to control endometrial cell migration during embryo implantation.\",\n      \"evidence\": \"RT-PCR, Western blot, ERK1/2 inhibition in fibroblasts; luciferase reporter and in vivo miR-126a-3p inhibition in mice\",\n      \"pmids\": [\"26403263\", \"26194885\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether FGF2 acts at the ITGA11 promoter or post-transcriptionally not resolved\", \"In vivo implantation phenotype not rescued by ITGA11 re-expression\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A ceRNA regulatory paradigm was established: multiple non-coding RNAs (FEZF1-AS1/miR-516b-5p, circRNA_100290/miR-29b-3p, circPDSS1/miR-515-5p) converge on ITGA11 to modulate its expression in cancer contexts, controlling proliferation, migration, EMT, and chemoresistance.\",\n      \"evidence\": \"Dual-luciferase reporter, RNA immunoprecipitation, knockdown/overexpression, and xenograft models in NSCLC and gastric cancer cells\",\n      \"pmids\": [\"33174014\", \"34182990\", \"36484486\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional contribution of ITGA11 itself versus other miRNA targets not individually dissected\", \"ceRNA axes not validated across independent labs\", \"Endogenous stoichiometry of ceRNA competition not assessed\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Genetic loss-of-function in Itga11-knockout mice demonstrated a non-redundant role in skin inflammation, with Itga11 deletion substantially reducing psoriasiform dermatitis severity, fibroblast numbers, and immune cell infiltration.\",\n      \"evidence\": \"Itga11−/− knockout mice with imiquimod-induced psoriasis, skin transcriptomics, immunohistochemistry, forward genetics across 13 inbred strains\",\n      \"pmids\": [\"37565309\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the phenotype is fibroblast-intrinsic or involves immune cell-expressed ITGA11 not resolved\", \"Downstream signaling pathway mediating immune recruitment not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"ITGA11 on PDGFRα+ cancer-associated fibroblasts was shown to directly bind E-selectin (SELE) on lymphatic endothelial cells, activating SRC–pVEGFR3–MAPK signaling to drive lymphangiogenesis and facilitate cancer cell intravasation — establishing a cell-cell adhesion function beyond classical collagen binding.\",\n      \"evidence\": \"Single-cell RNA-seq, spatial transcriptomics, PDGFRα+ITGA11+ CAF-specific deficient mouse model, 910-case clinical cohort\",\n      \"pmids\": [\"38428409\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of ITGA11–SELE interaction not determined\", \"Whether beta-1 subunit is required for SELE binding not tested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"ITGA11 was positioned as a key effector of the FAK/PI3K/AKT pathway in osteogenic differentiation: overexpression in bone marrow MSCs under hypoxia promoted osteogenesis while inhibiting proliferation and angiogenesis, and LIPUS-mediated ITGA11 upregulation enhanced osseointegration in vivo.\",\n      \"evidence\": \"Gain- and loss-of-function in rat BMSCs, in vivo rat femur implant model with micro-CT and signaling pathway analysis\",\n      \"pmids\": [\"39566247\", \"39755586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct collagen-binding requirement for osteogenic signaling not tested\", \"Pathway specificity relative to other integrins not established\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"ITGA11 was shown to promote myoblast differentiation through FAK/Paxillin–Akt–GSK3β signaling, and glucocorticoid receptor-mediated transcriptional suppression of ITGA11 was identified as the mechanism of dexamethasone-induced differentiation arrest.\",\n      \"evidence\": \"Overexpression/siRNA, Western blot, GR antagonist RU486, sheep fetal myoblasts\",\n      \"pmids\": [\"41720752\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether GR directly binds the ITGA11 promoter not demonstrated\", \"Applicability to human myogenesis not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of ITGA11's dual ligand recognition (collagen I and E-selectin), the identity of transcription factors acting on its promoter elements, and the fibroblast-intrinsic versus immune cell-mediated contributions to its inflammatory phenotype remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No crystal structure of ITGA11 I-domain with collagen or SELE\", \"Trans-acting factors for the defined promoter silencer/enhancer unknown\", \"Conditional cell-type-specific knockouts in inflammation not reported\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [0, 9]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 3, 9]},\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [8, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [8, 9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 9, 10, 11, 12]},\n      {\"term_id\": \"R-HSA-1500931\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [10, 11, 12]}\n    ],\n    \"complexes\": [\n      \"alpha11beta1 integrin\"\n    ],\n    \"partners\": [\n      \"ITGB1\",\n      \"SELE\",\n      \"FAK\",\n      \"PDGFRA\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}