Affinage

ITGB1

Integrin beta-1 · UniProt P05556

Round 2 corrected
Length
798 aa
Mass
88.4 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGB1 encodes integrin beta-1, the common beta subunit of the VLA integrin subfamily that heterodimerizes with at least five distinct alpha subunits to form cell-surface adhesion receptors for extracellular matrix ligands including fibronectin, collagen, and laminin (PMID:3546305, PMID:2958481). Its cytoplasmic domain directly binds alpha-actinin, FAK, paxillin, and ILK, linking integrin-ECM engagement to actin cytoskeleton organization and activating downstream PI3K/AKT/GSK-3 signaling; mechanical force induces catch-bond behavior and a conformational switch that controls fibronectin bond strength and FAK phosphorylation (PMID:2116421, PMID:7657702, PMID:8538749, PMID:9736715, PMID:19179533, PMID:19564406). ITGB1 surface complexes with tetraspanins (CD81, CD63) and CD38 regulate adhesion, exosome uptake, and immune cell function, while ITGB1 mRNA stability is controlled by m6A epitranscriptomic regulators (ALKBH5, FTO, YTHDF2, IGF2BP1) and multiple miRNAs, with downstream FAK/Src/AKT/YAP1/NF-κB signaling governing cell migration, EMT, radioresistance, chemoresistance, and immune escape (PMID:8757325, PMID:24667602, PMID:36632222, PMID:34098071, PMID:33613118, PMID:37386737).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1987 High

    Identification of ITGB1 as the shared 130 kDa beta subunit across five VLA heterodimers and determination of its primary sequence established the molecular identity of a major integrin subfamily and defined the integrin superfamily through sequence homology.

    Evidence Immunoprecipitation, cross-linking, 2D gel analysis, and cDNA cloning in human cell lines

    PMID:2958481 PMID:3546305

    Open questions at the time
    • Tertiary structure of the full-length beta1 subunit was not resolved
    • Alpha-subunit pairing rules and tissue-specific expression remained undefined
  2. 1990 High

    Direct binding of the beta1 cytoplasmic domain to alpha-actinin, and subsequently to FAK and paxillin, provided the molecular basis for how integrin ligation is transmitted to the actin cytoskeleton and to intracellular kinase signaling at focal adhesions.

    Evidence Affinity chromatography and solid-phase binding with synthetic beta1 cytoplasmic peptides; domain mapping of FAK and paxillin binding sites

    PMID:2116421 PMID:7657702

    Open questions at the time
    • Structural basis of simultaneous multi-partner binding on the short beta1 tail was not established
    • In vivo stoichiometry of the beta1 cytoplasmic domain signaling complex remained unknown
  3. 1996 High

    Discovery of ILK as a beta1 cytoplasmic domain-binding kinase that phosphorylates the beta1 tail and disrupts epithelial architecture placed a serine/threonine kinase directly downstream of integrin engagement, later shown to bridge beta1 to PI3K-dependent AKT and GSK-3 phosphorylation.

    Evidence Yeast two-hybrid screen, in vitro kinase assay, co-IP in mammalian cells, overexpression phenotypes; subsequent PI3K inhibitor and in vitro kinase reconstitution studies

    PMID:8538749 PMID:9736715

    Open questions at the time
    • Whether ILK functions as a true kinase versus a pseudokinase scaffold remains debated
    • Full reconstitution of the ILK-PINCH-parvin complex on beta1 was not achieved in these studies
  4. 1996 High

    Association of beta1 integrins with tetraspanins (CD81, CD63, CD82) and later with CD38 revealed that integrin function at the cell surface is organized in tetraspanin-enriched microdomains that modulate adhesion, signaling, and exosome uptake.

    Evidence Reciprocal co-IP, confocal colocalization, mutant integrin analysis; CD38 co-capping and adhesion assays in CLL cells; CD29/CD81 knockdown effects on exosome uptake

    PMID:22289918 PMID:24667602 PMID:8757325

    Open questions at the time
    • Structural basis of tetraspanin-integrin interaction is unresolved
    • Whether CD38 modulates all beta1 heterodimers or only VLA-4 is unclear
  5. 2000 High

    The crystal structure of the alpha2 I domain bound to a collagen peptide provided the first atomic-resolution view of how a beta1-containing integrin engages its ECM ligand, revealing divalent cation-dependent coordination and conformational propagation relevant to affinity regulation.

    Evidence X-ray crystallography at 2.1 Å with mutagenesis validation

    PMID:10778855

    Open questions at the time
    • Full-length alpha-beta heterodimer structure was not determined
    • Conformational changes in the beta1 subunit itself during ligand binding were inferred, not directly observed
  6. 2009 High

    Single-molecule force measurements demonstrated that alpha5beta1 exhibits catch-bond behavior under mechanical load and that myosin II-generated tension controls a conformational switch regulating fibronectin bond strength and FAK phosphorylation, establishing the biophysical basis of integrin mechanotransduction.

    Evidence AFM-based single-bond lifetime measurements, myosin II inhibition, conformation-specific antibodies, FAK phosphorylation assays

    PMID:19179533 PMID:19564406

    Open questions at the time
    • Catch-bond behavior has not been demonstrated for all beta1 heterodimer pairs
    • How mechanical force is transmitted through the beta1 transmembrane domain to the cytoplasmic tail at atomic resolution is unknown
  7. 2010 Medium

    ITGB1 was established as a direct target of multiple miRNAs (miR-124, miR-134-5p, miR-497) through 3′ UTR luciferase reporter validation, revealing a major layer of post-transcriptional regulation that controls ITGB1 protein levels in cancer and bone biology.

    Evidence Luciferase reporter assays, miRNA overexpression/inhibition, rescue experiments, in vivo models

    PMID:21112327 PMID:34589278 PMID:35691339

    Open questions at the time
    • Combinatorial effects of multiple miRNAs on ITGB1 in a single cell type are not defined
    • Physiological relevance of individual miRNA-ITGB1 axes outside cancer contexts is limited
  8. 2021 Medium

    ITGB1 mRNA stability was shown to be controlled by m6A epitranscriptomic modification: demethylases ALKBH5 and FTO remove m6A to stabilize ITGB1 mRNA, while YTHDF2 promotes its degradation, and IGF2BP1 phase separation enhances its stability, placing ITGB1 at a convergence point of multiple m6A reader/writer/eraser pathways.

    Evidence m6A-RIP, RNA pulldown, RIP-qPCR, mRNA decay assays, phase separation imaging, ITGB1 rescue experiments across ovarian cancer, gastric cancer, diabetic retinopathy, and oral cancer models

    PMID:34098071 PMID:34277426 PMID:36632222 PMID:39891203

    Open questions at the time
    • Whether m6A regulation of ITGB1 operates in non-pathological contexts is unknown
    • The relative quantitative contribution of different m6A effectors to ITGB1 protein output has not been determined in a single system
  9. 2021 Medium

    Functional studies in cancer models demonstrated that ITGB1 activates a YAP1-EMT axis to confer radioresistance and an NF-κB axis to confer chemoresistance, expanding ITGB1 downstream signaling beyond the canonical FAK/AKT cascade to include drug-resistance and immune-escape programs.

    Evidence shRNA knockdown in radioresistant NSCLC lines, co-IP of PD-L1/ITGB1, NF-κB activation assays, EMT marker analysis, colony formation

    PMID:33613118 PMID:37386737

    Open questions at the time
    • Direct versus indirect activation of YAP1 by ITGB1 is not mechanistically resolved
    • Whether PD-L1/ITGB1 interaction is constitutive or therapy-induced requires clarification
  10. 2023 Medium

    ITGB1 was identified as a functional receptor for paracrine signals from the tumor microenvironment — including TIMP-1/CD63, THBS4, POSTN, MUC5AC, and GMFG — that activate FAK/Src/STAT3 cascades to promote migration, invasion, and immune remodeling, establishing ITGB1 as a central hub for stromal-tumor communication.

    Evidence Co-IP, mass spectrometry interactome, spatial transcriptomics, antibody blockade, rescue experiments, xenograft and autochthonous mouse models

    PMID:30635444 PMID:32567740 PMID:35219699 PMID:35884543 PMID:36291767 PMID:39207055

    Open questions at the time
    • Whether these diverse ligands compete for the same binding site on ITGB1 or engage distinct heterodimers is unknown
    • Quantitative ligand affinities and in vivo ligand hierarchies remain undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural model of full-length beta1 integrin in complex with its cytoplasmic partners under force, and the relative contributions of transcriptional, epigenetic, miRNA, and m6A regulatory inputs to ITGB1 protein output in normal versus disease tissues, remain unresolved.
  • No full-length heterodimer structure with cytoplasmic partners under physiological load
  • Integrated quantitative model of ITGB1 regulation across transcriptional, post-transcriptional, and post-translational layers is lacking
  • In vivo contributions of individual alpha-beta1 pairings to specific tissue phenotypes are incompletely dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 6 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 5 GO:0031012 extracellular matrix 3
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
ACTN1CD274CD38CD63CD81ILKPTK2PXN
Complex memberships
Tetraspanin-enriched microdomain (CD81/CD63/CD82)VLA integrin heterodimers (alpha/beta1)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The beta subunit of the VLA (Very Late Antigen) integrin family was characterized as a common 130,000 molecular weight subunit shared across five distinct cell surface heterodimers (VLA-1 through VLA-5), establishing ITGB1 as the common beta chain of the VLA integrin subfamily. Immunoprecipitation, chemical cross-linking, 2D gel analysis, V8 protease cleavage, cell surface radiolabeling The Journal of biological chemistry High 3546305
1987 The amino acid sequence of the human fibronectin receptor (alpha5beta1 integrin) was determined from cDNA; the beta1 subunit (778 aa) contains a transmembrane domain, a short cytoplasmic domain, and a fourfold cysteine-rich repeat in the ectodomain, and shares 44–47% homology with beta3 and beta2 integrin subunits, defining the integrin superfamily of adhesion receptors. cDNA cloning and sequence analysis The Journal of cell biology High 2958481
1990 The cytoplasmic domain of beta1 integrin directly binds alpha-actinin in vitro, providing a molecular link between the integrin and the actin cytoskeleton at focal contacts. Affinity chromatography with synthetic beta1 cytoplasmic domain peptide, solid-phase binding assay, immunoblot The Journal of cell biology High 2116421
1989 Antibody crosslinking of the VLA-4 beta1 subunit (CD29) on CD4+ T cells inhibits CD4+ cell proliferation triggered by CD2 or CD3, and binding to activated T cells leads to increased cyclic AMP levels comparable to forskolin, indicating that beta1 integrin mediates negative signaling in T cell activation. Antibody inhibition of lymphocyte proliferation, cAMP measurement Nature Medium 2566120
1995 The cytoplasmic domain of beta1 integrin directly binds both focal adhesion kinase (FAK/pp125FAK) and paxillin in vitro; FAK binds via its N-terminal non-catalytic domain to sequences distinct from those bound by alpha-actinin, and paxillin binding is independent of FAK binding. In vitro binding assay with synthetic beta1 cytoplasmic domain peptide and cell lysates; domain mapping The Journal of cell biology High 7657702
1996 Integrin-linked kinase (ILK), a 59K serine/threonine protein kinase, was identified as a direct binding partner of the beta1 integrin cytoplasmic domain; ILK phosphorylates a beta1 cytoplasmic domain peptide in vitro, co-immunoprecipitates with beta1 in mammalian cells, and its overexpression disrupts epithelial architecture, inhibits adhesion, and induces anchorage-independent growth. Yeast two-hybrid screen, in vitro kinase assay with beta1 peptide, co-immunoprecipitation, overexpression in mammalian cells Nature High 8538749
1996 CD81 (TAPA-1) and other transmembrane-4 superfamily members (CD53, CD63, CD82) specifically associate with alpha4beta1 (VLA-4, CD49d/CD29) integrin, colocalizing in cell surface clusters; this association does not require the alpha4 cytoplasmic domain and is not influenced by divalent cations or integrin-activating antibodies, but is abolished by two alpha4 adhesion-deficient mutations (D346E, D408E). Co-immunoprecipitation, reciprocal immunoprecipitation, confocal microscopy colocalization, mutant integrin analysis Journal of immunology High 8757325
1995 A hamster monoclonal antibody (HM beta1-1) against mouse beta1 integrin (CD29) blocked adhesion of mouse tumor cell lines to collagen, laminin, and fibronectin, and inhibited T cell proliferation when combined with anti-LFA-1, demonstrating that mouse beta1 integrins mediate VLA-dependent adhesion to ECM and co-stimulatory functions in T cell activation. Antibody blocking of cell adhesion to ECM substrates, T cell proliferation inhibition assay International immunology Medium 7547709
1998 ILK activity is stimulated by fibronectin-mediated cell attachment and by insulin in a PI3K-dependent manner; phosphatidylinositol(3,4,5)trisphosphate directly stimulates ILK in vitro; ILK phosphorylates GSK-3 in vitro and inhibits its activity in vivo; kinase-active ILK phosphorylates PKB/AKT on serine-473, placing ILK downstream of PI3K as a regulator of both AKT and GSK-3 downstream of beta1 integrin engagement. In vitro kinase assay, PI3K inhibitor treatment, constitutively active PI3K overexpression, co-IP, GSK-3 and AKT phosphorylation measurements Proceedings of the National Academy of Sciences of the United States of America High 9736715
2000 Crystal structure of the alpha2 I domain of integrin alpha2beta1 in complex with a triple-helical collagen peptide (GFOGER motif) was determined at 2.1 Å; collagen glutamate completes the metal coordination sphere of the I domain; ligand binding induces conformational changes that propagate from the upper surface to the opposite pole, suggesting a mechanism for affinity regulation and signal transduction by the beta1-containing collagen receptor. X-ray crystallography with functional validation by mutagenesis and binding studies Cell High 10778855
2000 Activation of EphA2 kinase suppresses beta1 integrin function and causes FAK dephosphorylation; EphA2 is constitutively associated with FAK, and upon ephrin-A1 stimulation SHP2 is recruited to EphA2, followed by dephosphorylation of FAK and paxillin, revealing crosstalk between Eph receptors and beta1 integrin-FAK signaling. Co-immunoprecipitation, phosphorylation assays, cell spreading and migration assays, integrin activity assays Nature cell biology High 10655584
2003 TIMP-2 binds to alpha3beta1 integrin on endothelial cells and induces a decrease in total protein tyrosine phosphatase (PTP) activity associated with beta1 integrin subunits, and dissociation of SHP-1 from beta1, with concomitant increased PTP activity at FGFR-1 and KDR, thereby inhibiting angiogenic factor-induced endothelial cell proliferation independently of MMP inhibition. Integrin-blocking antibodies, PTP activity assays, co-immunoprecipitation, in vitro proliferation and in vivo angiogenesis assays Cell High 12887919
2003 Extracellular galectin-3 binds to CD29 (beta1 integrin) and CD7 on T cell lines and activated T cells, inducing apoptosis via the mitochondrial pathway (cytochrome c release and caspase-3 activation, but not caspase-8); this effect is inhibited by lactose, indicating carbohydrate-dependent binding of galectin-3 to beta1 integrin as a death receptor. Lactose inhibition assay, antibody blocking, co-immunoprecipitation, cytochrome c release assay, caspase activation measurement Cancer research Medium 14678989
2009 Alpha5beta1 integrin (containing the beta1 subunit) switches between relaxed and tensioned states in response to myosin II-generated cytoskeletal force; this switch controls the alpha5beta1-fibronectin bond strength by engaging the synergy site in fibronectin and is required for FAK phosphorylation, linking mechanical force to beta1 integrin-mediated signaling. Single-molecule force measurements, myosin II inhibition, integrin conformation-specific antibodies, FAK phosphorylation assay Science High 19179533
2009 Single-bond lifetime measurements between fibronectin and alpha5beta1 integrin demonstrate catch bonds: force in the 10–30 pN range prolongs bond lifetimes; cation changes and activating antibodies shift the catch bond behavior, implicating force-assisted headpiece activation in catch bond formation by beta1 integrins. Atomic force microscopy, single-molecule force spectroscopy, integrin-Fc fusion proteins The Journal of cell biology High 19564406
2010 MicroRNA-124 directly targets the 3' UTR of ITGB1 mRNA, downregulates ITGB1 protein expression, and reduces adherence and motility of oral squamous cell carcinoma cells, establishing ITGB1 as a functional target of miR-124 regulation. 3' UTR luciferase reporter assay, miRNA overexpression, Western blot, adhesion and motility assays FEBS letters Medium 21112327
2011 Mechanical loading reduces CD29 (ITGB1) surface expression on mesenchymal stromal cells (MSCs) and decreases their migration; specific inhibition of CD29 phenocopies the loading-induced migration defect; focal adhesion kinase and Src-family kinases were identified as candidate downstream targets of CD29 in MSC migration. Mechanical loading, flow cytometry, antibody-mediated CD29 inhibition, migration assay, FAK/Src kinase analysis European cells & materials Medium 21732280
2012 The CD49d/CD29 (VLA-4, alpha4beta1) integrin complex constitutively associates with CD38 in CLL cells; CD38 enhances CD49d-mediated adhesion to VCAM-1 and fibronectin substrates, promotes Vav-1 phosphorylation and F-actin redistribution at adhesion sites, and increases resistance to apoptosis in adherent CD49d+CD38+ CLL cells. Co-capping, co-immunoprecipitation, cell adhesion assays, phospho-Vav-1 measurement, F-actin imaging, apoptosis assays Leukemia Medium 22289918
2013 Sox10 transcription factor regulates beta1 integrin (Itgb1) expression levels; compound Sox10/Itgb1 mutant mice show increased intestinal aganglionosis and more severe neuronal network disorganization than single mutants, with reduced migration speed and altered directionality of enteric neural crest cells (ENCCs), demonstrating a genetic interaction between Sox10 and Itgb1 in enteric nervous system development. Genetic epistasis with double mutant mice, video-microscopy migration tracking, immunostaining, Sox10 overexpression Developmental biology Medium 23608456
2014 Radiation increases cellular uptake of exosomes through formation of a CD29 (ITGB1)/CD81 complex on the mesenchymal stem cell surface; knockdown of CD29 completely inhibits radiation-induced exosome uptake, and knockdown of CD81 inhibits basal uptake, establishing the CD29/CD81 complex as a receptor mediating radiation-enhanced exosome internalization. siRNA knockdown, confocal colocalization, exosome uptake quantification, surface protein complex formation analysis Biochemical and biophysical research communications Medium 24667602
2015 Knockdown of CD29 (ITGB1) alone, or combined with CD49f knockdown, in cancer stem cells from Brca1-mutant tumors reduces cell migration, with combined knockdown producing a profound block in migration, demonstrating critical and overlapping roles of CD29 and CD49f in cancer stem cell migration. shRNA knockdown, cell migration assay, allograft nude mouse metastasis model Oncogene Medium 24317509
2015 CD29 (ITGB1) overexpression in hepatocellular carcinoma cells activates ILK, increases Akt Ser473 phosphorylation and mTORC1 expression, decreases E-cadherin, increases fibronectin and vimentin (EMT markers), and enhances resistance to radiation and cisplatin, while CD29 silencing sensitizes cells to these treatments. Adenoviral overexpression and shRNA silencing, Western blot for ILK/AKT/mTOR/EMT markers, MTT viability, xenograft mouse model Medical oncology Medium 25805567
2018 CD31 upregulates ITGB1 expression in hepatocellular carcinoma cells and promotes EMT and metastasis via the ITGB1-FAK-Akt signaling pathway. Western blot, siRNA silencing, invasion/migration assays, xenograft model Cancer letters Medium 29746931
2018 VLA-4 (CD49d/CD29, alpha4beta1) integrin can be inside-out activated by BCR triggering in CLL cells, reinforcing adhesion; ibrutinib reduces constitutive VLA-4 activation but this can be overcome by BCR triggering via a BTK-independent PI3K-dependent mechanism. In vitro and in vivo ibrutinib treatment, inside-out activation assays, cell adhesion assays, PI3K inhibitor experiments The Journal of experimental medicine Medium 29301866
2019 TIMP-1 secreted by Toxoplasma gondii-challenged dendritic cells binds CD63, which signals through ITGB1 (CD29) to activate FAK, SRC, and PI3K, driving hypermotile amoeboid migration of dendritic cells; shRNA silencing of ITGB1 or pharmacological inhibition of FAK, SRC, and PI3K abrogated hypermotility. shRNA gene silencing of TIMP-1, CD63, and ITGB1; antibody blockade; pharmacological FAK/SRC/PI3K inhibition; migration assays Journal of cell science Medium 30635444
2019 In zebrafish, loss of itgb1 (itgβ1.b-/-) causes increased ECM deposition (laminin and collagen) at the muscle basement membrane and reduced myotomal elasticity; RGD peptide inhibition of ITGB1 in a laminin-α2-deficient MDC1A model similarly increases ECM deposition and improves muscle fibre stability, establishing that ITGB1 signaling regulates ECM homeostasis at the muscle basement membrane. Zebrafish genetic knockout, immunostaining, passive force analysis, RGD peptide injection in disease model Human molecular genetics Medium 30566586
2019 RAD9 controls ITGB1 protein levels in human prostate cancer cells; RAD9 or ITGB1 silencing sensitizes cells to ionizing radiation; combined RAD9 knockdown with irradiation reduces ITGB1 protein by an additional 50%; fibronectin-mediated radioprotection (via beta1 integrin-ECM contact) is abolished by RAD9 knockdown, establishing RAD9 as an upstream regulator of ITGB1-dependent radioresistance. RNA interference, Western blot, colony formation assay, cell cycle analysis, PARP-1 cleavage assay The Prostate Medium 25111005
2020 THBS4 (thrombospondin 4) interacts with ITGB1 via co-immunoprecipitation and regulates the FAK/PI3K/AKT pathway to promote hepatocellular carcinoma EMT, proliferation, and metastasis. Co-immunoprecipitation, Western blot, immunofluorescence, xenograft model, EMT marker analysis FASEB journal Medium 32567740
2021 ALKBH5, an m6A demethylase, removes m6A modification from ITGB1 mRNA, suppressing YTHDF2-mediated m6A-dependent ITGB1 mRNA degradation; this leads to increased ITGB1 protein, FAK and Src phosphorylation, and enhanced lymphangiogenesis and lymph node metastasis in ovarian cancer. Hypoxia induces HIF-1α → ALKBH5 → ITGB1 → FAK/Src axis. RNA pulldown, RIP-qPCR, co-immunoprecipitation, m6A-RIP-qPCR, luciferase reporter assay, in vitro and in vivo functional studies Theranostics Medium 36632222
2021 KAT1 activates YTHDF2 transcription via histone acetylation of its promoter; YTHDF2 in turn triggers m6A-dependent ITGB1 mRNA degradation, suppressing ITGB1 expression and the downstream FAK/PI3K/AKT signaling pathway in diabetic retinopathy models. ChIP-seq/histone acetylation assay, YTHDF2 knockdown, m6A-mRNA degradation assay, Western blot for FAK/PI3K/AKT, in vivo mouse model Pharmacological research Medium 34098071
2021 ITGB1 knockdown in radioresistant NSCLC cells enhances radiation-induced DNA damage, G2/M arrest, and apoptosis; ITGB1 induces radioresistance by promoting DNA repair and by activating YAP1, which drives EMT; silencing ITGB1 suppresses YAP1 expression and intracellular translocation. shRNA knockdown, immunofluorescence, colony formation, flow cytometry, Western blot for YAP1 and EMT markers International journal of biological sciences Medium 33613118
2021 ITGB1 drives hepatocellular carcinoma cell cycle progression through a PXN/YWHAZ/AKT axis; ITGB1 siRNA knockdown downregulates paxillin (PXN) and 14-3-3ζ (YWHAZ), delays cell cycle progression, and impairs aggressive tumor cell behavior. siRNA knockdown, Western blot, immunostaining, cell cycle analysis, colony formation, migration assay, xenograft model Frontiers in cell and developmental biology Medium 34977001
2021 miR-497 directly targets CDC42 and ITGB1 in gastric cancer cells; miR-497 overexpression inhibits focal adhesion formation by reducing ITGB1 expression and suppressing the CDC42/ITGB1/FAK/paxillin/AKT signaling cascade; CDC42 restoration rescues the metastasis-suppressing effect of miR-497. miRNA overexpression, gene rescue, Western blot for FAK/PXN/AKT phosphorylation, in vivo metastasis assay, miR-497 knockout mice Molecular therapy. Nucleic acids Medium 34589278
2021 FTO, an m6A demethylase, promotes gastric cancer metastasis by decreasing the m6A modification level of ITGB1 mRNA, thereby increasing ITGB1 protein expression; ITGB1 overexpression partially rescues the migration/invasion suppression caused by FTO knockdown. FTO knockdown/overexpression, m6A-RIP quantification, Western blot, migration/invasion assays, ITGB1 rescue experiment Frontiers in oncology Medium 34277426
2021 ITGB1-DT lncRNA interacts with EZH2, reduces H3K27me3 levels at the ITGB1 promoter, and thereby activates ITGB1 expression; increased ITGB1 then activates Wnt/β-catenin signaling and its target MYC; MYC in turn transcriptionally activates ITGB1-DT, forming a positive feedback loop in lung adenocarcinoma. RNA-protein co-IP (EZH2-lncRNA), ChIP for H3K27me3 at ITGB1 promoter, luciferase reporter, Western blot, gain/loss-of-function experiments, in vivo metastasis Frontiers in cell and developmental biology Medium 33763420
2022 TIMP-1 secreted by cancer-associated fibroblasts (CAFs) binds CD63 and cooperates with integrin beta1 (ITGB1) to activate STAT3 and ERK1/2 in breast cancer cells; knockdown of ITGB1 (or CD63 or TIMP-1 or STAT3) blocks CAF-induced migration and growth, establishing a TIMP-1/CD63/ITGB1/STAT3 feedback loop that drives breast cancer cell behavior. siRNA knockdown of TIMP-1, CD63, ITGB1, STAT3; recombinant TIMP-1 treatment; Western blot for STAT3/ERK1/2 activation; migration assays Cancers Medium 36291767
2022 MUC5AC secreted by pancreatic cancer cells binds CD44 and ITGB1 on adipose-derived mesenchymal stem cells, promoting CD44/ITGB1 (CD29) clustering that activates Rac1 and drives AD-MSC migration toward tumor sites; Rac1 inhibition abolishes migration, and MUC5AC depletion reduces stromal remodeling. Mass spectrometry MUC5AC interactome, flow cytometry for CD44/CD29 clustering, live-cell imaging, Rac1 inhibitor, autochthonous mouse model (KC, KCM), co-implantation xenografts Gastroenterology Medium 35219699
2022 DDR2 in cancer-associated fibroblasts regulates periostin (POSTN) expression, which in turn promotes ovarian cancer invasion through ITGB1; DDR2/POSTN-expressing CAFs enhance mesothelial clearance and invasion three-fold, and DDR2-depleted/POSTN-overexpressing CAFs increased tumor burden in vivo. Co-culture assays, siRNA/shRNA depletion, mesothelial clearance assay, invasion assay, mouse tumor burden model Cancers Medium 35884543
2022 miR-134-5p directly targets Itgb1 mRNA (confirmed by luciferase reporter) in bone marrow macrophages; Itgb1 knockdown reverses the pro-osteoclastogenic effect of miR-134-5p antagomir; the miR-134-5p/Itgb1 axis modulates MAPK pathway proteins p-p38 and p-ERK to regulate osteoclast differentiation. Luciferase reporter assay, miRNA agomir/antagomir transfection, Itgb1 siRNA, MAPK signaling analysis, OVX mouse model The Journal of biological chemistry Medium 35691339
2023 USP51 deubiquitinates and stabilizes PD-L1 in chemoresistant NSCLC cells; stabilized PD-L1 directly binds ITGB1 at the membrane (confirmed by co-IP and pulldown), and PD-L1/ITGB1 interaction activates NF-κB to promote chemoresistance; flavonoid DHM inhibits USP51 and reduces PD-L1 stability, decreasing ITGB1-NF-κB chemoresistance. Co-immunoprecipitation, pulldown, deubiquitinase activity assay (Ub-AMC), cellular thermal shift assay, surface plasmon resonance, tissue microarray, Western blot Cancer communications Medium 37386737
2023 The RNA-binding protein RPS7 stabilizes LOXL2 mRNA by binding AUUUA motifs in the 3'UTR; LOXL2 then maintains ITGB1 protein stability and activates ITGB1-mediated FAK/SRC signaling to promote hepatocellular carcinoma adhesion, migration, invasion, and lung metastasis. RIP, RNA pulldown, dual luciferase reporter, nascent RNA capture, RNA decay assay, CRISPR-Cas9 KO, Western blot for FAK/SRC, in vivo lung metastasis Journal of experimental & clinical cancer research Medium 38326908
2023 Hypoxia-induced lncRNA NNT-AS1 promotes pancreatic cancer immune escape by increasing ITGB1 mRNA stability in a METTL3-HuR-dependent m6A manner; NNT-AS1 silencing reduces ITGB1 expression and reverses hypoxia-induced immune escape, while ITGB1 overexpression rescues the effect of NNT-AS1 knockdown. ChIP, RIP, dual-luciferase reporter assay, xenograft model, CD8+ T cell co-culture assay, ELISA Experimental cell research Medium 37659467
2024 ITGB1 upregulation is associated with acquired resistance to osimertinib and MEK inhibitors in EGFR-mutant NSCLC; combined treatment with MEK inhibitor and DDR inhibitors downregulates ITGB1 and increases cell death, and an interplay between ITGB1 and DDR family proteins was identified in mediating EMT-associated drug resistance. Western blot, flow cytometry, siRNA knockdown, drug combination experiments in resistant cell lines Scientific reports Low 38177190
2024 CD248 promotes osteosarcoma metastasis by enhancing the interaction between ITGB1 and ECM proteins CYR61 and fibronectin, which activates the FAK-paxillin focal adhesion pathway; co-immunoprecipitation confirmed CD248-ITGB1 interaction, and CD248 knockdown reduces ITGB1-ECM engagement, FAK-paxillin activation, focal adhesion formation, and lung metastasis. RNA-seq, co-immunoprecipitation, Western blot, immunofluorescence, migration/invasion assay, nude mouse lung metastasis model BMC cancer Medium 36997926
2024 GMFG, secreted by ERS-CAF cells under hypoxic IER2 upregulation, directly binds ITGB1 on tumor cells (confirmed by spatial proximity and functional assays); ITGB1 inhibition attenuates chordoma malignant progression, partially reversible by exogenous GMFG, and ITGB1-high tumors correlate with increased SPP1+ macrophage density, implicating ITGB1 in tumor-macrophage crosstalk. Single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, DIA proteomics, multiplexed immunofluorescence, ITGB1 antibody blockade, GMFG binding assay Advanced science Medium 39207055
2025 CircRNF13 binds the m6A reader protein IGF2BP1, inhibiting its ubiquitin-mediated degradation and promoting its phase separation; this enhanced IGF2BP1 phase separation increases ITGB1 mRNA stability through m6A modification in an IGF2BP1-dependent manner, promoting oral cancer cisplatin resistance. RNA immunoprecipitation, ubiquitination assay, phase separation imaging, m6A quantification, in vitro and in vivo tumor growth, ITGB1 mRNA stability assay Molecular cancer Medium 39891203

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2019 Blood-Brain Barrier: From Physiology to Disease and Back. Physiological reviews 1645 30280653
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Integrins. Cell and tissue research 1256 19693543
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1996 Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 958 8538749
1998 Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proceedings of the National Academy of Sciences of the United States of America 922 9736715
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 Structural basis of collagen recognition by integrin alpha2beta1. Cell 819 10778855
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
1990 An interaction between alpha-actinin and the beta 1 integrin subunit in vitro. The Journal of cell biology 777 2116421
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
1987 Amino acid sequence of the human fibronectin receptor. The Journal of cell biology 565 2958481
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