Affinage

ITGA1

Integrin alpha-1 · UniProt P56199

Length
1179 aa
Mass
130.8 kDa
Annotated
2026-06-10
92 papers in source corpus 30 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGA1 (CD49a) encodes the alpha-1 subunit of the integrin VLA-1, which pairs in a 1:1 acid-labile, heavily glycosylated heterodimer with a beta-1 subunit on activated T cells (PMID:2415516) and functions as a divalent-cation-dependent receptor for interstitial and basement-membrane collagens (types I–IV), C1q, and laminin through a non-RGD binding mechanism (PMID:2229189, PMID:1807406). Ligand engagement requires Mg2+ or Mn2+ and is inhibited by Ca2+, and adhesion can be activated through the beta-1 subunit or stimulated by PKC (PMID:7516898, PMID:10457223); ligand specificity is further tuned in a cell-type-specific manner, with VLA-1 serving as a principal laminin and/or collagen receptor depending on context (PMID:7898055). Beyond adhesion, VLA-1 transduces intracellular signals upon clustering (PMID:8025956). Functionally, VLA-1-mediated collagen attachment anchors memory and tissue-resident T cells in nonlymphoid tissues, sustaining their persistence, motility, and recall responses while being dispensable for trafficking into those tissues (PMID:14975239, PMID:20200271, PMID:37269830), and it likewise maintains gut intraepithelial lymphocytes and supports collagen-dependent T cell proliferation (PMID:10805967). The same collagen-IV-dependent contact extends MDSC–T cell interactions to enable immune suppression (PMID:33584706) and drives NK cell dysfunction, with CD49a blockade restoring cytotoxicity in the tumor microenvironment (PMID:30756436, PMID:39570767). ITGA1 also restrains TGFβ-receptor-II signaling in chondrocytes to protect against osteoarthritis (PMID:37649532), promotes fibrosis in kidney disease (PMID:12368200), and drives microglial neuroinflammation via a PGAM5/NLRP3 axis (PMID:41462565). In multiple cancers ITGA1 promotes migration and invasion through downstream FAK, STAT3, and PI3K-Akt signaling (PMID:40083708, PMID:40939856, PMID:42020859). Its expression is controlled both transcriptionally—by SRF at a promoter CArG box, by E2F1 and TEAD1, and by RUNX2/RUNX3 in cytotoxic TRM differentiation—and epigenetically by promoter CpG methylation that silences it in the megakaryocyte lineage (PMID:17669516, PMID:37269830, PMID:38169150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1985 High

    Established the molecular identity of VLA-1 as a defined integrin heterodimer, answering what the CD49a antigen physically is.

    Evidence Cross-linking, immunoprecipitation, SDS-PAGE and peptide mapping on activated T cells

    PMID:2415516

    Open questions at the time
    • Did not define the ligand specificity of the complex
    • Beta subunit identity not yet placed in the integrin family
  2. 1991 High

    Defined the ligand repertoire and binding mode of VLA-1, showing it is a cation-dependent, non-RGD collagen/laminin receptor.

    Evidence Affinity-purified VLA-1 reconstituted into liposomes, tested against multiple ECM substrates with RGD peptide and cation manipulation

    PMID:1807406 PMID:2229189

    Open questions at the time
    • Did not map the collagen-binding site on the alpha-1 subunit
    • Conformational basis of activation not addressed
  3. 1994 Medium

    Demonstrated that VLA-1 adhesion is regulated by divalent cation switching and can transduce outside-in signals, not merely mediate static attachment.

    Evidence Cell adhesion assays with Mg2+/Mn2+/Ca2+ manipulation, activating anti-beta1 antibody, and antibody-induced IL-2R expression

    PMID:7516898 PMID:8025956

    Open questions at the time
    • Downstream signaling intermediates not identified
    • Mechanism of cation-dependent affinity change not resolved structurally
  4. 1995 Medium

    Showed VLA-1 expression is dynamically regulated by activation and quiescence states and by inflammatory cytokines, framing it as an inducible context-dependent receptor.

    Evidence Flow cytometry, immunoprecipitation and Northern blot on T cells, fibroblasts, and monocytes under defined stimulation/redox conditions

    PMID:3106495 PMID:3292271 PMID:7589148

    Open questions at the time
    • Transcription factors driving induction not identified at this stage
    • Cell-type heterogeneity of regulation not mechanistically explained
  5. 2000 High

    Genetic loss-of-function established VLA-1 as required in vivo for gut intraepithelial lymphocyte maintenance and collagen-dependent T cell proliferation.

    Evidence VLA-1 null mice with lymphocyte counting and adhesion/proliferation assays

    PMID:10805967

    Open questions at the time
    • Whether retention vs. proliferation drives the IEL deficit unresolved
    • Signaling pathway behind collagen-dependent proliferation unknown
  6. 2010 High

    Defined VLA-1 as a tissue-retention factor for memory CD8 and CD4 T cells, distinguishing tissue anchoring from trafficking.

    Evidence Antibody blockade and alpha1-/- mice in influenza challenge models with tissue-compartment flow cytometry and recall assays

    PMID:14975239 PMID:20200271

    Open questions at the time
    • Molecular link between collagen adhesion and anti-apoptotic survival not detailed
    • Contribution of signaling vs. physical anchoring not separated
  7. 2007 High

    Revealed dual transcriptional/epigenetic control of ITGA1, identifying an SRF CArG box and lineage-specific CpG methylation silencing in megakaryocytes.

    Evidence Bisulfite sequencing, promoter-LUC reporters, 5-aza-2'-deoxycytidine demethylation and TPO differentiation time course

    PMID:17669516

    Open questions at the time
    • The de novo methyltransferase responsible not identified
    • How SRF activity intersects with methylation status unresolved
  8. 2020 High

    Distinguished CD49a's role in TRM locomotion and persistence from its dispensability for trafficking, and identified TGF-β/IL-12/IL-15 plus RUNX2/RUNX3 as inducers of the CD49a+ cytotoxic TRM program.

    Evidence Intravital imaging and CD49a-deficient mice; RUNX2/RUNX3 knockdown with in vitro IL-15/TGF-β differentiation and transcriptomics

    PMID:32439709 PMID:32877667 PMID:37269830

    Open questions at the time
    • Direct RUNX binding at the ITGA1 locus not mapped
    • How CD49a mechanically drives dendritic motility unresolved
  9. 2023 High

    Genetic epistasis established that ITGA1 normally restrains TGFBR2 signaling, defining a protective role against osteoarthritis and fibrosis.

    Evidence itga1-/- mice with cartilage-specific TGFBR2 depletion, histological OA scoring and pain assays; antibody neutralization in glomerulonephritis

    PMID:12368200 PMID:37649532

    Open questions at the time
    • Biochemical mechanism by which ITGA1 dampens TGFBR2 not defined
    • Whether direct receptor cross-talk or indirect ECM remodeling mediates restraint unknown
  10. 2021 High

    Showed VLA-1/collagen-IV contact extends suppressive immune-cell interactions, implicating it in MDSC-mediated T cell suppression.

    Evidence Itga1-/- mice with intravital two-photon microscopy and in vivo suppression assays

    PMID:33584706

    Open questions at the time
    • Signaling consequence of prolonged contact in MDSCs not defined
    • Generalizability beyond splenic red pulp unaddressed
  11. 2025 Medium

    Connected CD49a to NK cell exhaustion and microglial neuroinflammation, positioning it as a therapeutic target in tumors and Parkinson's disease.

    Evidence CD49a knockout and antibody blockade across tumor models with anti-PD-L1 combination; conditional microglial Itga1 knockdown with PGAM5/NLRP3 and obtustatin antagonism

    PMID:39570767 PMID:41462565

    Open questions at the time
    • Mechanism linking CD49a engagement to NK exhaustion program not defined
    • How ITGA1 controls PGAM5 expression in microglia unresolved
  12. 2025 Medium

    Defined ITGA1 as a pro-tumorigenic effector across cancers acting through FAK, STAT3, and PI3K-Akt, with transcriptional and m6A-dependent control of its expression.

    Evidence Knockdown/inhibition (obtustatin) with rescue in retinoblastoma, glioblastoma, osteosarcoma; E2F1/TEAD1 ChIP and RBM15B MeRIP/mRNA-stability assays

    PMID:28264467 PMID:38169150 PMID:40083708 PMID:40939856 PMID:42020859

    Open questions at the time
    • Whether collagen ligation or ligand-independent signaling drives tumor effects unclear
    • Integration of FAK/STAT3/PI3K-Akt outputs not unified across tumor types

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single collagen/laminin receptor produces opposing outcomes—T cell retention, immune suppression, tissue protection, and tumor progression—depending on cell type remains unresolved.
  • No unified model linking ligand context to divergent downstream signaling
  • Structural basis of cell-type-specific ligand specificity uncharacterized
  • Relative contribution of physical anchoring vs. signaling not separated across systems

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3
Partners
ITGB1PGAM5TGFBR2THBS1
Complex memberships
VLA-1 (integrin alpha1beta1)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 VLA-1 (ITGA1/CD49a) is a heterodimeric protein complex composed of an Mr 210,000 alpha-1 subunit in acid-labile association with an Mr 130,000 beta subunit, forming a 1:1 stoichiometric heterodimer on activated T cells. The alpha-1 and beta subunits contain substantial sialic acid and N-linked carbohydrate, and are highly non-homologous to each other by peptide mapping. Cross-linking experiments, immunoprecipitation, SDS-PAGE, neuraminidase/endoglycosidase F digestion, one-dimensional peptide mapping The Journal of biological chemistry High 2415516
1990 Purified VLA-1 integrin from human smooth muscle (195 kD alpha + 130 kD beta subunits) binds type I, II, III, and IV collagens, C1q, and laminin in a Ca2+/Mg2+-dependent manner via liposome adhesion assays. It does not bind gelatin, fibronectin, or thrombospondin. Affinity chromatography on collagen-Sepharose, liposome adhesion assay, quantitative immunoblotting The Journal of cell biology High 2229189
1991 Purified VLA-1 from human smooth muscle interacts with interstitial collagens (types I, II, III) and basement membrane proteins (type IV collagen and laminin) via a Ca2+/Mg2+-dependent mechanism in liposome assays; does not interact with fibronectin, thrombospondin, or albumin. The RGD peptide does not inhibit binding, indicating a non-RGD binding mechanism. Denaturation of type I collagen reduces binding 5–7-fold. Liposome binding assay with purified VLA-1 integrin, inhibition experiments with RGD peptide and cation chelation Biokhimiia (Moscow, Russia) High 1807406
1987 VLA-1 expression on T cells is downregulated by mitogenic stimulation (PHA, ConA) in a reversible manner, whereas VLA-2 is not similarly suppressed. Repetitive restimulation with alloantigen or anti-CD3 increases the VLA-2:VLA-1 ratio. These changes are intrinsic to homogeneous T cell lines, not due to subpopulation shifts, indicating cell-cycle/activation-state-dependent regulation of VLA-1 expression. Flow cytometry, immunoprecipitation of T cell lines under defined stimulation conditions Journal of immunology Medium 3106495
1988 Cell quiescence induced by low serum (0.5%) causes a 10–28-fold increase in VLA-1 expression on normal human fibroblasts with a corresponding decrease in VLA-2 and VLA-3. These changes are reversible upon re-stimulation with serum and persist after proliferation has stopped, indicating that VLA-1 upregulation is linked to quiescence rather than cell-cycle transitions per se. Flow cytometry, immunoprecipitation, quantitative comparison under defined serum conditions Experimental cell research Medium 3292271
1994 VLA-1-mediated adhesion of NB100 neuroblastoma cells to collagen type I is supported by Mg2+ (mM) or Mn2+ (µM) but not Ca2+ alone; Ca2+ inhibits Mg2+-supported adhesion. VLA-1 can be directly activated by the stimulatory anti-β1 monoclonal antibody TS2/16 to promote collagen adhesion. Cell adhesion assay with divalent cation manipulation, blocking antibody experiments, monoclonal antibody activation FEBS letters Medium 7516898
1994 VLA-1 (CD49a) on T cells functions as a specific collagen IV receptor: antibody blockade of CD49a (mAb 1B3.1) inhibited adhesion to collagen IV but not fibronectin, and Mg2+ supported VLA-1-mediated spreading on collagen IV. Cross-linking of VLA-1 with plastic-bound antibody selectively induced IL-2R expression on γδ T cell clones, demonstrating VLA-1 can transduce intracellular signals. Cell adhesion assay, antibody blocking, cation manipulation, IL-2R expression by flow cytometry Cellular immunology Medium 8025956
1995 In glomerular epithelial cells (GEC), VLA-1 and VLA-2 cooperate for adhesion to laminin, while only VLA-2 is used for collagen adhesion. In mesangial cells, VLA-1 is the primary laminin receptor and both VLA-1 and VLA-2 support collagen adhesion. This demonstrates cell-type-specific modulation of VLA-1 ligand binding specificity. Monoclonal antibody blocking of cell adhesion to extracellular matrix proteins, ELISA, immunocytochemistry Laboratory investigation Medium 7898055
1999 Integrin alpha1beta1 (VLA-1) is the primary collagen receptor on human intestinal intraepithelial lymphocytes (IELs): antibody blockade of alpha1 (CD49a) and beta1 subunits inhibited IEL adhesion to collagen type I by ~82% and to type IV by ~94%. Adhesion was upregulated by PKC stimulation (phorbol ester) and was dependent on divalent cations (Mn2+/Mg2+ supportive, Ca2+ inhibitory), consistent with canonical integrin activation. 51Cr-labeled cell adhesion assay, antibody blocking, pharmacological stimulation (PKC activators/inhibitors), divalent cation manipulation Immunology High 10457223
2000 VLA-1 null mice have a ~50% reduction in gut intraepithelial lymphocytes (IELs) with normal peripheral blood and lymphoid organ lymphocyte distribution and unchanged γδ:αβ IEL ratios. IL-2-stimulated splenocytes from VLA-1 null mice show deficient adhesion to fibrillar and basement membrane collagen and reduced proliferation on collagen substratum, demonstrating that VLA-1 is required for IEL maintenance in the gut and for collagen-dependent T cell proliferation. Genetic knockout mouse (VLA-1 null), cell counting, adhesion assays, proliferation assays Cellular immunology High 10805967
2004 VLA-1 (alpha1beta1 integrin) is required for retention of influenza-specific CD8 memory T cells in the lung and nonlymphoid tissues. Antibody blockade or genetic deficiency of VLA-1 decreased virus-specific CTL in lung and other nonlymphoid tissues while increasing them in the spleen, and impaired secondary heterosubtypic immunity, demonstrating that VLA-1 mediates T cell retention in tissues via ECM attachment. Antibody blockade, genetic knockout mice, flow cytometry, challenge infection model, tissue distribution analysis Immunity High 14975239
2007 The ITGA1 gene locus is regulated by DNA CpG methylation: the ITGA1 promoter is fully methylated at 19 CpG sites in megakaryocytic (MK) cells that do not express alpha1beta1, and completely demethylated in expressing cells. In vitro methylation of ITGA1 suppresses transcription. Treatment with the DNA demethylating agent 5-aza-2'-deoxycytidine (but not the HDAC inhibitor Trichostatin A) induces de novo ITGA1 expression in MK cells. Progressive CpG methylation of ITGA1 occurs during thrombopoietin-induced megakaryocyte differentiation. The ITGA1 promoter also contains a CArG box bound by serum response factor (SRF). Sodium bisulfite genomic sequencing, promoter-LUC reporter assays, 5-aza-2'-deoxycytidine treatment, qPCR, Northern blot, transcription factor binding analysis Biochimica et biophysica acta High 17669516
2002 VLA-1 antibody blockade in a rat model of crescentic glomerulonephritis reduced glomerular and tubulointerstitial scarring, decreased type IV collagen and ED(A) fibronectin deposition, and increased matrix metalloproteinase-9 expression in glomeruli. This demonstrates that VLA-1 mediates renal fibrosis, and that its neutralization promotes matrix degradation via MMP-9 upregulation. Monoclonal antibody treatment in vivo (rat model), histology, immunohistochemistry, biochemical markers The American journal of pathology Medium 12368200
2010 VLA-1 (alpha1beta1) is required for the accumulation of CD4+ tissue memory T cells in the airways after influenza infection. Fewer memory/effector CD4+ T cells were recovered from airways of alpha1-/- mice but lymphoid tissues were unaffected. Airway CD49a+CD4+ cells expressed reduced apoptosis markers and provided rapid IFN-γ responses upon secondary challenge. Genetic knockout mice (alpha1-/-), flow cytometry, intracellular cytokine staining, apoptosis markers, secondary challenge infection model Journal of immunology High 20200271
1995 LPS and IFN-γ rapidly induce de novo expression of alpha1/beta1 (VLA-1) integrin on monocytes, detectable on the membrane within 12 hours, with induction of alpha1 mRNA. This induction is dependent on the cellular redox state (inhibited by antioxidants). Monocyte-deactivating cytokines (IL-4, IL-10) only minimally inhibit this upregulation. Flow cytometry, Northern blot, pharmacological inhibition with antioxidants and cytokines European journal of immunology Medium 7589148
2002 VLA-1 on MS patient-derived, myelin antigen-reactive T cell lines mediates adhesion to collagen IV (the major collagenous constituent of vascular basement membranes) and active transmigration through collagen IV gels toward TNF-α; both processes were inhibited almost completely by anti-VLA-1 mAb. Ionizing radiation abrogated VLA-1-mediated collagen IV adhesion, suggesting radiation-induced integrin clustering impairs VLA-1 function. Cell adhesion assay, transwell transmigration assay, antibody blocking, irradiation experiments, immunofluorescence of integrin clustering Journal of clinical immunology Medium 12078857
2017 ITGA1 (integrin alpha1) is required for collagen-induced tumorigenic potential in pancreatic ductal adenocarcinoma (PDAC) cells. ITGA1 depletion impairs collagen/ITGA1 signaling that supports survival of ALDH1+ stem-like cancer cells and cooperates with TGFβ to drive gemcitabine resistance. ITGA1 is also required for TGFβ/collagen-induced EMT and metastasis. siRNA/shRNA knockdown of ITGA1, colony/invasion assays, stem cell marker analysis (ALDH1), drug resistance assays, metastasis assays Scientific reports Medium 28855593
2017 E2F1 transcription factor directly upregulates ITGA1 expression in hepatocellular carcinoma cells, as demonstrated by dual luciferase reporter assay and chromatin immunoprecipitation. d-ICD inhibits E2F1 expression and thereby suppresses ITGA1-mediated HCC cell migration and invasion. Dual luciferase reporter assay, chromatin immunoprecipitation (ChIP), wound healing assay, transwell invasion assay, Western blot, qRT-PCR International journal of molecular sciences Medium 28264467
2019 CD49a (ITGA1) on human decidual NK cells suppresses cytotoxicity: CD49a neutralizing antibody upregulated perforin, granzyme B, and IFN-γ expression, increased killing activity (51Cr release assay), and downregulated dNK cell migration and adhesion. A newly identified lncRNA (lnc-49a) was shown to positively regulate CD49a expression in primary human NK cells. CD49a neutralizing antibody, flow cytometry, 51Cr release cytotoxicity assay, lncRNA microarray, primary human NK cells American journal of reproductive immunology Medium 30756436
2020 CD49a (integrin alpha1) on lung TRM CD8+ T cells facilitates cell locomotion (motility) in vitro and in vivo, but is not required for trafficking of T cells to the lung. CD49a supports CD8+ TRM persistence within skin and regulates epidermal TRM dendritic extensions. TGF-β and IL-12 can induce CD49a expression on CD8+ T cells in vitro. CD49a expression is not required for the primary CD8+ T cell response, migration across the epidermal basement membrane, or TRM positioning in basal epidermis. Live imaging, intravital microscopy, genetic knockout (CD49a-deficient mice), flow cytometry, in vitro migration assay, cytokine induction assay PNAS / Cell reports High 32439709 32877667
2023 RUNX2 and RUNX3 transcription factors are required for CD49a expression and cytotoxic transcriptional programs in human epidermal CD8+CD103+CD49a+ TRM cells. In vitro stimulation of circulating CD8+ memory T cells with IL-15 and TGF-β induced CD49a expression and cytotoxic profiles in a RUNX2- and RUNX3-dependent manner, establishing these TFs as writers of the CD49a+ TRM differentiation program. RUNX2/RUNX3 knockdown (siRNA/shRNA), in vitro differentiation with IL-15 and TGF-β, transcriptome sequencing, paired skin/blood clonal analysis, flow cytometry Immunity High 37269830
2024 Loss of ITGA1 (and ITGA2) activates EMT via enhanced secretion and autocrine activation of TGFβ1 and nuclear targeting of YAP1 in prostate epithelial cells. The transcription factor TEAD1 directly regulates ITGA1 and ITGA2 expression in prostate cancer cells, and TEAD1 loss phenocopies dual integrin loss in vitro and in vivo. Genomic deletion, CRISPR/shRNA knockdown, in vitro EMT assays, in vivo tumorigenesis, TGFβ1 measurement, YAP1 nuclear localization, genome-wide co-expression analysis, ChIP/regulatory analysis Advanced science Medium 38169150
2021 VLA-1 (alpha1beta1/CD49a) adhesion to collagen IV is required for extended interaction times between activated MDSCs and effector T cells in the splenic red pulp, enabling effective T cell suppression. VLA-1-deficient A-MDSCs showed reduced interaction times with effector T cells on collagen IV (but not fibronectin) and reduced suppressive activity in vivo, without affecting MDSC motility or migration parameters. Itga1-/- knockout mice, intravital two-photon microscopy, in vitro and in vivo suppression assays, MDSC-T cell interaction timing, T cell proliferation and apoptosis assays Frontiers in immunology High 33584706
2023 Integrin alpha1beta1 (ITGA1) moderates TGFβ receptor II (TGFBR2) signaling in cartilage chondrocytes. Itga1-null mice develop earlier and more severe spontaneous knee osteoarthritis with increased baseline TGFBR2 activation and fibrosis. Cartilage-specific depletion of TGFBR2 in itga1-null mice attenuated OA progression, demonstrating a genetic epistasis relationship where ITGA1 normally dampens TGFBR2 signaling to protect against cartilage degeneration. Genetic knockout (itga1-/- mice), tamoxifen-induced cartilage-specific TGFBR2 depletion, histological OA scoring, pain behavior assays, TGFBR2 signaling pathway analysis Osteoarthritis and cartilage open High 37649532
2025 CD49a on NK cells mediates an exhausted/dysfunctional state in tumor-infiltrating NK cells. CD49a deficiency or antibody blockade slowed tumor growth and prolonged survival in multiple mouse tumor models, primarily through NK cell antitumor activity. Combination of anti-CD49a with anti-PD-L1 further enhanced antitumor efficacy. Genetic knockout (CD49a-/- and NK-specific CD49a-deficient mice), mAb blockade, multiple tumor models, survival analysis, NK cell functional assays Cancer immunology research High 39570767
2025 Microglial CD49a (ITGA1) drives neuroinflammation in Parkinson's disease models. Microglial-specific Itga1 knockdown attenuates hyperreactivity, preserves dopaminergic neurons, and improves motor deficits. Mechanistically, ITGA1 knockdown in microglia reduces PGAM5 expression, which ameliorates mitochondrial dysfunction and suppresses NLRP3 inflammasome assembly. The disintegrin obtustatin specifically antagonizes microglial CD49a and reproduces these protective effects. Conditional Itga1 knockdown, transcriptomic profiling of isolated microglia, NLRP3 inflammasome assays, mitochondrial function assays, obtustatin pharmacological antagonism, PD mouse models Advanced science Medium 41462565
2023 ITGA1 (integrin alpha1) promotes hepatocellular carcinoma cell migration and invasion in vitro, and this is regulated transcriptionally: E2F1 directly activates ITGA1 transcription (shown by ChIP), and ITGA1 partially mediates d-ICD-induced suppression of migration; overexpression of ITGA1 partially rescues migration inhibited by d-ICD treatment. Wound healing assay, transwell invasion assay, Western blot, qRT-PCR, rescue experiments with ITGA1 overexpression International journal of molecular sciences Medium 28264467
2025 RBM15B promotes ITGA1 mRNA stability through m6A modification in glioblastoma cells. Downregulation of RBM15B reduces ITGA1 m6A modification levels and decreases ITGA1 mRNA stability. ITGA1 overexpression activates the PI3K-Akt signaling pathway to promote GBM cell proliferation, migration, and invasion. Methylated RNA immunoprecipitation (MeRIP), actinomycin D mRNA stability assay, Western blot, PI3K-Akt pathway analysis, in vivo xenograft Discover oncology Medium 42020859
2025 Thrombospondin 1 (THBS1) promotes accumulation of ITGA1 (and ITGA6) on the osteosarcoma cell membrane in the early phase of dedifferentiation, which increases phosphorylation of FAK, RasGRF1, and MLC2, promoting cytoskeletal remodeling and pulmonary metastasis. Sphere formation assay, mRNA-seq, Western blot for FAK/RasGRF1/MLC2 phosphorylation, membrane protein fractionation, in vivo metastasis model International journal of biological sciences Medium 40083708
2025 ITGA1 knockdown or pharmacological inhibition with obtustatin impairs proliferation, migration, and clonogenicity of retinoblastoma (Y79) cells. Transcriptome analysis and Western blot identified STAT3 as a key downstream mediator of ITGA1 signaling; STAT3 agonist ML115 partially rescued the inhibitory effects of ITGA1 suppression. Lentiviral ITGA1 knockdown, obtustatin inhibition, transcriptome analysis, Western blot, STAT3 rescue experiments, in vivo xenograft Experimental eye research Medium 40939856
2024 ITGA1 promotes interstitial fibrosis in ADPKD: Pkd1nl/nl Itga1-/- double-knockout mice showed significantly reduced kidney volume, smaller cysts, reduced interstitial expansion, less collagen staining, and reduced myofibroblast marker expression compared to Pkd1nl/nl mice. Primary fibroblast cultures from Itga1-/- mice showed abrogated fibrogenic phenotype. Double-knockout mouse model, proteomics, kidney histology (Picrosirius red, α-SMA), primary fibroblast culture bioRxiv (preprint)preprint Medium
2017 ITGA1 expression is specifically suppressed in the megakaryocyte lineage through progressive CpG methylation of its promoter during thrombopoietin-induced megakaryocyte differentiation. The ITGA1 promoter contains a serum response factor (SRF)-binding CArG box. Neither PELO nor ITGA2 (the neighboring genes in the ITGA1-PELO-ITGA2 locus) undergo similar methylation during this process. Sodium bisulfite sequencing, LUC reporter assay, 5-aza-2'-deoxycytidine demethylation, Trichostatin A treatment, qPCR time course during megakaryocyte differentiation Biochimica et biophysica acta High 17669516

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin. Immunity 562 28214226
2004 The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity 254 14975239
1992 T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1. Arteriosclerosis and thrombosis : a journal of vascular biology 249 1531930
2015 Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells. Journal of immunology (Baltimore, Md. : 1950) 211 25672754
1985 VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. European journal of immunology 159 2986987
1985 Biochemical characterization of VLA-1 and VLA-2. Cell surface heterodimers on activated T cells. The Journal of biological chemistry 147 2415516
1990 Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development. The Journal of cell biology 142 2229189
2003 STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. Cell and tissue research 113 12883998
2020 TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection. Proceedings of the National Academy of Sciences of the United States of America 109 32439709
2003 Direct selection of human bone marrow mesenchymal stem cells using an anti-CD49a antibody reveals their CD45med,low phenotype. British journal of haematology 107 12877680
2020 CD49a Regulates Cutaneous Resident Memory CD8+ T Cell Persistence and Response. Cell reports 94 32877667
1988 T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA-1. Clinical immunology and immunopathology 90 3257425
2007 Collagen distribution and expression of collagen-binding alpha1beta1 (VLA-1) and alpha2beta1 (VLA-2) integrins on CD4 and CD8 T cells during influenza infection. Journal of immunology (Baltimore, Md. : 1950) 71 17372009
2017 ITGA1 is a pre-malignant biomarker that promotes therapy resistance and metastatic potential in pancreatic cancer. Scientific reports 68 28855593
2021 Prostate Cancer Peripheral Blood NK Cells Show Enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 Production and Secrete Monocyte-Recruiting and Polarizing Factors. Frontiers in immunology 67 33569050
2018 Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus. Frontiers in immunology 67 30079068
1995 Glomerular epithelial and mesangial cells differentially modulate the binding specificities of VLA-1 and VLA-2. Laboratory investigation; a journal of technical methods and pathology 59 7898055
2017 IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells. Immunity, inflammation and disease 51 28952190
2023 Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. Immunity 49 37269830
2007 Selection using the alpha-1 integrin (CD49a) enhances the multipotentiality of the mesenchymal stem cell population from heterogeneous bone marrow stromal cells. Journal of molecular histology 48 17694277
2021 Hsa_circ_0110757 upregulates ITGA1 to facilitate temozolomide resistance in glioma by suppressing hsa-miR-1298-5p. Cell death & disease 47 33674567
1987 Cell matrix adhesion-related proteins VLA-1 and VLA-2: regulation of expression on T cells. Journal of immunology (Baltimore, Md. : 1950) 47 3106495
2010 Identification of a unique population of tissue-memory CD4+ T cells in the airways after influenza infection that is dependent on the integrin VLA-1. Journal of immunology (Baltimore, Md. : 1950) 45 20200271
2006 Human and rodent bone marrow mesenchymal stem cells that express primitive stem cell markers can be directly enriched by using the CD49a molecule. Cell and tissue research 45 17109120
2000 Reduced gut intraepithelial lymphocytes in VLA1 null mice. Cellular immunology 45 10805967
1999 Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen. Immunology 45 10457223
1992 Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia. Leukemia 44 1588789
2003 Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells. The Journal of clinical investigation 37 14597770
1988 Regulation of proteins in the VLA cell substrate adhesion family: influence of cell growth conditions on VLA-1, VLA-2, and VLA-3 expression. Experimental cell research 37 3292271
1995 Monocyte activation: rapid induction of alpha 1/beta 1 (VLA-1) integrin expression by lipopolysaccharide and interferon-gamma. European journal of immunology 35 7589148
2021 CD49a Identifies Polyfunctional Memory CD8 T Cell Subsets that Persist in the Lungs After Influenza Infection. Frontiers in immunology 32 34566986
1990 Increased expression of laminin/collagen receptor (VLA-1) on epithelium of inflamed human intestine. Journal of clinical pathology 31 2341567
2017 Expression and role of VLA-1 in resident memory CD8 T cell responses to respiratory mucosal viral-vectored immunization against tuberculosis. Scientific reports 30 28842633
1994 Functional regulation of the human integrin VLA-1 (CD49a/CD29) by divalent cations and stimulatory beta 1 antibodies. FEBS letters 30 7516898
2022 Human-Induced CD49a+ NK Cells Promote Fetal Growth. Frontiers in immunology 29 35185911
2011 Combined blockade of VEGFR-3 and VLA-1 markedly promotes high-risk corneal transplant survival. Investigative ophthalmology & visual science 29 21715348
2002 Treatment with an antibody to VLA-1 integrin reduces glomerular and tubulointerstitial scarring in a rat model of crescentic glomerulonephritis. The American journal of pathology 29 12368200
1994 Functional role of VLA-1 (CD49A) in adhesion, cation-dependent spreading, and activation of cultured human T lymphocytes. Cellular immunology 29 8025956
1989 A novel monoclonal antibody, 1B3.1, binds to a new epitope of the VLA-1 molecule. Cellular immunology 29 2475259
2022 Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma. Metabolic brain disease 27 36301458
2017 Derivate Isocorydine (d-ICD) Suppresses Migration and Invasion of Hepatocellular Carcinoma Cell by Downregulating ITGA1 Expression. International journal of molecular sciences 27 28264467
2019 CD49a regulates the function of human decidual natural killer cells. American journal of reproductive immunology (New York, N.Y. : 1989) 26 30756436
2021 Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8+ T Cells. Cancer immunology research 25 33619119
1987 Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis. Annals of the rheumatic diseases 22 2827591
2007 Transcriptional and epigenetic regulation of the integrin collagen receptor locus ITGA1-PELO-ITGA2. Biochimica et biophysica acta 21 17669516
1993 T lymphocytes in giant cell arteritic lesions are polyclonal cells expressing alpha beta type antigen receptors and VLA-1 integrin receptors. Clinical and experimental immunology 20 8383021
2024 Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 38169150
2021 Selection for CD26- and CD49A+ Cells From Pluripotent Stem Cells-Derived Islet-Like Clusters Improves Therapeutic Activity in Diabetic Mice. Frontiers in endocrinology 18 34025576
2007 Polymorphisms and haplotypes of integrinalpha1 (ITGA1) are associated with bone mineral density and fracture risk in postmenopausal Koreans. Bone 17 17931993
2018 Formation and phenotypic characterization of CD49a, CD49b and CD103 expressing CD8 T cell populations in human metastatic melanoma. Oncoimmunology 15 30288359
2020 CD49a+CD49b+ NK cells induced by viral infection reflect an activated state of conventional NK cells. Science China. Life sciences 14 32335843
2023 Antiviral Responses of Tissue-resident CD49a+ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease. American journal of respiratory and critical care medicine 13 36170617
2018 Cytokine-Based Generation of CD49a+Eomes-/+ Natural Killer Cell Subsets. Frontiers in immunology 13 30319610
2017 The SNP-set based association study identifies ITGA1 as a susceptibility gene of attention-deficit/hyperactivity disorder in Han Chinese. Translational psychiatry 12 28809852
2015 Langerhans Cells Suppress CD49a+ NK Cell-Mediated Skin Inflammation. Journal of immunology (Baltimore, Md. : 1950) 12 26209621
1999 The epidermotropic mycosis fungoides associated alpha1beta1 integrin (VLA-1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells. Journal of cutaneous pathology 12 10082395
2019 CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans. Frontiers in immunology 11 31231382
2014 CD49a promotes T-cell-mediated hepatitis by driving T helper 1 cytokine and interleukin-17 production. Immunology 11 24164540
2013 ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population. World journal of gastroenterology 11 24124332
2008 Synovial VLA-1+ T cells display an oligoclonal and partly distinct repertoire in rheumatoid and psoriatic arthritis. Clinical immunology (Orlando, Fla.) 11 18456562
2002 Interaction of disease-related antigen-reactive T-cell lines from multiple sclerosis patients with type IV collagen: role of integrin VLA-1 and effects of irradiation. Journal of clinical immunology 11 12078857
1992 Genetic mapping of the integrin alpha 1 gene (Vla1) to mouse chromosome 13. Genomics 9 1427867
2018 Taste receptor T1R1/T1R3 promotes the tumoricidal activity of hepatic CD49a+ CD49b- natural killer cells. European journal of immunology 7 30259960
2010 Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction. Thrombosis and haemostasis 7 20076856
2025 Thrombospondin 1 Promotes Cytoskeleton Remodeling, Dedifferentiation, and Pulmonary Metastasis through ITGA1 and ITGA6 in Osteosarcoma. International journal of biological sciences 6 40083708
2023 Linc00662 m6A promotes the progression and metastasis of pancreatic cancer by activating focal adhesion through the GTF2B-ITGA1-FAK pathway. American journal of cancer research 6 37293163
2019 Synergistic anticancer effect of Grb2 and ITGA1 on cancer cells highly expressing Grb2 through suppressing ERK phosphorylation. International journal of clinical and experimental pathology 6 31933732
2024 ITGA1 Promotes Glioma Cell Proliferation and Affects Immune Cell Infiltration in Low-Grade Glioma. Mediators of inflammation 5 39502752
2022 Melanocyte-specific CD49a+ CD8+ T cells in vitiligo lesion potentiate to maintain activity during systemic steroid therapy. The Journal of dermatology 5 36514908
2022 Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX. Medicina (Kaunas, Lithuania) 5 36556936
2020 Characterization of Rhesus Macaque Liver-Resident CD49a+ NK Cells During Retrovirus Infections. Frontiers in immunology 5 32849583
2020 Novel genetic variants of SYK and ITGA1 related lymphangiogenesis signaling pathway predict non-small cell lung cancer survival. American journal of cancer research 5 32905494
2025 ITGA1, the alpha 1 subunit of integrin receptor, is a novel marker of drug-resistant senescent melanoma cells in vitro. Archives of toxicology 4 40202610
2023 Depleting transforming growth factor beta receptor 2 signalling in the cartilage of itga1-null mice attenuates spontaneous knee osteoarthritis. Osteoarthritis and cartilage open 4 37649532
2023 High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma. Heliyon 4 38107324
2025 CD49a Targeting Enhances NK Cell Function and Antitumor Immunity. Cancer immunology research 3 39570767
2025 Targeting Microglial CD49a Inhibits Neuroinflammation and Demonstrates Therapeutic Potential for Parkinson's Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 41462565
2021 VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp. Frontiers in immunology 3 33584706
2007 The effect of blockade of tumor necrosis factor alpha on VLA-1+ T-cells in rheumatoid arthritis patients. Journal of clinical immunology 3 17891451
2024 CD4+ T cell help during early acute hepacivirus infection is critical for viral clearance and the generation of a liver-homing CD103+CD49a+ effector CD8+ T cell subset. PLoS pathogens 2 39392861
2026 Resident CD49a+CD103+NKG2C+ NK cells restrict HIV infection in human lymphoid tissue explants. Science advances 1 41576166
2025 CD49a+ NK cells promote esophageal cancer development by inducing MDCSs infiltration via GM-CSF. British journal of cancer 1 40437020
2016 Effects of VLA-1 Blockade on Experimental Inflammation in Mice. The Kobe journal of medical sciences 1 27578034
2006 Expression of VLA1, VLA2 and VLA3 Integrin Molecules in Uterine Endometrium of Infertile Women with Unexplained Aetiology in Ahwaz-Iran. Iranian journal of immunology : IJI 1 18685175
2026 Dual-targeted NIR-II AIE theranostic nanoparticles disrupt HNRNPC-driven ITGA1+ myCAFs differentiation and immune evasion in oral squamous cell carcinoma. Biomaterials 0 41702227
2026 CD133/CD49a discriminate between human pluripotent stem cell-derived pancreatic beta and alpha cells. Stem cell reports 0 41791382
2026 RBM15B enhancing ITGA1 mRNA stability can accelerate glioblastoma tumorigenesis via the PI3K-Akt pathway. Discover oncology 0 42020859
2026 CD39+CD49a+CD103+ cytotoxic tissue-resident natural killer cells infiltrate and control solid epithelial tumor growth in mice. Science translational medicine 0 42090477
2026 CD49a expression defines a metabolically robust, cytokine-biased liver NK cell subset in rhesus macaques during lentivirus infection. Immunology and cell biology 0 42203213
2025 Luteolin Alleviates Diabetic Foot Ulcers Through Improving KDM4C/ITGA1-mediated Functional Impairments of AGEs-Induced Senescent Endothelial Cell. Journal of biochemical and molecular toxicology 0 40778546
2025 Therapeutic targeting of ITGA1 delayed retinoblastoma progression through suppression of STAT3 signaling. Experimental eye research 0 40939856
1991 [Isolation and characteristics of ligand specificity of VLA-1 integrin from human smooth muscles]. Biokhimiia (Moscow, Russia) 0 1807406

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