Affinage

ITGAV

Integrin alpha-V · UniProt P06756

Length
1048 aa
Mass
116.0 kDa
Annotated
2026-06-10
96 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGAV (integrin αV, CD51) encodes an αV integrin subunit that pairs with β subunits to form RGD-binding adhesion receptors mediating attachment to extracellular matrix and matricellular ligands including vitronectin, SPP1/osteopontin, periostin, thrombospondin-1, and collagen-associated scaffolds, and it transduces these contacts into intracellular signaling controlling proliferation, migration, invasion, stem-cell behavior, and tissue homeostasis (PMID:7542504, PMID:28250242, PMID:27905395, PMID:39304722, PMID:20121756). Outside-in signaling through αV integrins engages divergent pathways: periostin–ITGAV ligation suppresses FAK/PI3K/AKT to enforce hematopoietic stem cell quiescence via p27Kip1 (PMID:27905395), CD51 binds TGF-β receptors and amplifies TGF-β/SMAD signaling to confer cancer stem-cell and invasive traits (PMID:27593923, PMID:40739706), and ITGAV feeds a Hippo/YAP-TAZ feedback loop in which TAZ drives ITGAV transcription and ITGAV in turn sustains nuclear YAP/TAZ and actin stress-fiber assembly (PMID:31904487). ITGAV is also a node in non-adhesive proteolytic signaling: γ-secretase cleaves CD51 to release a nuclear intracellular domain (CD51-ICD) that acts as a transcriptional co-activator, partnering with NR4A3 to drive neurotropic genes in colorectal cancer and inducing oxidative-phosphorylation genes to promote hepatocellular carcinoma invasion, with periostin driving the cleavage event (PMID:37174090, PMID:37604269). FURIN-mediated maturation of cytosolic ITGAV is required for lysosomal function and lipophagic flux in astrocytes, and αV-dependent noncanonical autophagy operates in germinal-center and memory B cells (PMID:41376284, PMID:36016494). ITGAV transcription is directly controlled by Runx2, TAZ, SOX11, CASZ1, and a LGALS3BP–JunB axis, and repressed by p53 via Sp1/Sp3 (PMID:37403784, PMID:31904487, PMID:38534932, PMID:36777515, PMID:40578967, PMID:29743605). Biallelic human loss-of-function ITGAV variants cause a syndrome of eye/brain malformations, inflammatory bowel disease, and immune dysregulation linked to disrupted TGF-β and αVβ3 immune signaling (PMID:39526957).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 Low

    Establishing the gene's chromosomal location and protein product provided the foundation for mechanistic study of the vitronectin-receptor αV subunit.

    Evidence FISH mapping to 2q31→q32 and cDNA/genomic characterization of the 150-kDa subunit

    PMID:10965141 PMID:7678549

    Open questions at the time
    • chromosomal localization alone establishes no function
    • no signaling or ligand engagement defined
  2. 1995 Medium

    Identifying functional αvβ3 on differentiated mast cells and its vitronectin binding defined ITGAV as an adhesion receptor for matrix ligands in immune-lineage cells.

    Evidence Adhesion and antibody-blocking assays in SCF-cultured human fetal mast cells

    PMID:7542504

    Open questions at the time
    • downstream signaling not addressed
    • no in vivo relevance shown
  3. 2000 Medium

    Demonstrating that an RGD-less coxsackievirus mutant still binds αvβ3 showed the receptor engages ligands through both RGD-dependent and RGD-independent modes.

    Evidence Binding studies on αvβ3-expressing and chimeric CHO cells with blocking antibodies and vitronectin competition

    PMID:10773347

    Open questions at the time
    • the RGD-independent contact residues on ITGAV not mapped
    • physiological ligands using this mode not enumerated
  4. 2005 Medium

    Discovery that αvβ3 binds endothelial Thy-1/CD90 extended ITGAV's ligand repertoire beyond classical matrix proteins to a cell-surface counter-receptor mediating transendothelial migration.

    Evidence Reciprocal purified-protein and transfected-cell binding plus flow/static adhesion blockade in melanoma

    PMID:15897908

    Open questions at the time
    • intracellular signaling consequence not defined
    • single-lab finding
  5. 2016 High

    Genetic models defined opposing context-dependent ITGAV signaling outputs: periostin–ITGAV suppression of FAK/PI3K/AKT maintains HSC quiescence, while ITGAV restrains adipogenic differentiation via TAZ.

    Evidence Reciprocal Postn-KO and Itgav conditional-KO mice with HSC repopulation assays; siRNA/overexpression in adipose-derived stem cells

    PMID:27363302 PMID:27905395

    Open questions at the time
    • how the same receptor selects FAK inhibition versus TAZ regulation is unresolved
    • ligand-specific signaling thresholds not defined
  6. 2016 Medium

    Showing CD51 binds TGF-β receptors and amplifies TGF-β/SMAD signaling linked ITGAV directly to cancer stem-cell and invasive phenotypes.

    Evidence Co-IP of CD51–TGF-β receptor, siRNA knockdown, sphere assays and in vivo tumor models in colorectal cancer

    PMID:27593923

    Open questions at the time
    • stoichiometry/structure of the CD51–TGFβR complex unknown
    • whether engagement requires β-subunit pairing not addressed
  7. 2018 Medium

    Identifying p53/Sp1/Sp3 repression and epigenetic demethylation control of ITGAV revealed that its expression is tightly regulated transcriptionally to gate stemness and differentiation programs.

    Evidence Reporter assays and ChIP in prostate cancer; bisulfite sequencing and osteogenic assays in mesenchymal cells

    PMID:29743605 PMID:30219480

    Open questions at the time
    • interplay of activating versus repressive regulators in a single cell context not integrated
    • direct p53 occupancy versus indirect Sp-mediated effect not fully separated
  8. 2019 Medium

    Showing macrophage CD51 confers stemness on neighboring tumor cells via TGF-β1/Smad2/3 paracrine signaling established a cell-non-autonomous, microenvironmental role for ITGAV.

    Evidence siRNA knockdown in macrophages with co-culture and Smad2/3 pathway readouts in pancreatic cancer

    PMID:31199988

    Open questions at the time
    • the ligand engaging macrophage CD51 not identified
    • single-lab co-culture model
  9. 2020 Medium

    Defining a TAZ→ITGAV→nuclear YAP/TAZ positive-feedback loop showed ITGAV both responds to and amplifies Hippo pathway activity through actin remodeling.

    Evidence RNAi of TAZ/YAP/ITGAV, actin staining, migration/invasion and nuclear fractionation in HCC

    PMID:31904487

    Open questions at the time
    • mechanism coupling ITGAV adhesion to YAP/TAZ nuclear retention not detailed
    • TAZ-specific versus YAP selectivity at the promoter not structurally resolved
  10. 2023 High

    Multiple transcription factors were shown to bind the ITGAV promoter directly, establishing Runx2, SOX11, and CASZ1 as drivers that route ITGAV into fibrosis, EMT, and metastasis programs.

    Evidence ChIP/ChIP-seq plus knockdown and in vivo models (Runx2 in hepatic stellate cell fibrosis; SOX11 in HNSCC; CASZ1 in lung cancer)

    PMID:36777515 PMID:37403784 PMID:38534932

    Open questions at the time
    • combinatorial control by these factors in a single tissue not addressed
    • whether they regulate specific αV/β heterodimers unknown
  11. 2023 Medium

    Discovery that γ-secretase cleaves CD51 to a nuclear ICD that co-activates NR4A3 redefined ITGAV as a signaling molecule acting in the nucleus, not only at the membrane.

    Evidence γ-secretase cleavage assay, CD51-ICD/NR4A3 Co-IP, reporter assays and pharmacological γ-secretase inhibition in colorectal cancer

    PMID:37174090

    Open questions at the time
    • full ICD target gene network beyond NTRK1/NTRK3/SEMA3E not mapped
    • single-lab interaction
  12. 2024 High

    The CD51-ICD axis was extended in HCC where periostin drives cleavage and the ICD induces oxidative-phosphorylation genes, explaining why surface-only inhibitors fail and motivating combined γ-secretase blockade.

    Evidence Cleavage and nuclear ICD assays, RNA-seq, periostin-KO mice, patient-derived organoids/xenografts with cilengitide+LY3039478

    PMID:37604269

    Open questions at the time
    • proportion of ITGAV signaling routed through ICD versus surface adhesion not quantified across tissues
    • regulation of cleavage by β-subunit pairing unknown
  13. 2024 High

    ITGAV was identified as a node integrating matricellular and innate-immune cues into NF-κB and TGF-β/THBS1 signaling, broadening its pro-tumor signaling beyond canonical FAK/SMAD routes.

    Evidence NET-DNA pull-down/MS and ChIP in cholangiocarcinoma; THBS1/ITGAV/TβRI Co-IP with CRISPR/siRNA and xenografts in CRPC

    PMID:38326837 PMID:39304722

    Open questions at the time
    • whether the same heterodimer mediates NET-DNA and THBS1 binding unclear
    • direct versus scaffold-mediated NF-κB activation not fully separated
  14. 2024 High

    Biallelic human loss-of-function variants causally linked ITGAV to a multisystem disorder, anchoring its physiological roles in TGF-β and αVβ3 immune signaling in vivo.

    Evidence Human genetics with patient-cell functional studies, RNA-seq, and zebrafish itgav deletion recapitulating retinal/brain, microglial, and colitis phenotypes

    PMID:39526957

    Open questions at the time
    • tissue-specific contributions of distinct αV heterodimers to the syndrome not dissected
    • genotype–phenotype correlation across variants limited
  15. 2025 High

    FURIN-dependent maturation of cytosolic ITGAV was shown to be required for lysosomal function and lipophagy, revealing a proteolytic-maturation requirement distinct from surface integrin assembly.

    Evidence IP-MS substrate identification, cleavage-site mutagenesis, lipophagic flux/lipidomics, and rescue with mature versus mutant ITGAV in FURIN-deficient astrocytes/mice

    PMID:41376284

    Open questions at the time
    • how the FURIN-matured form supports lysosomal/lipophagic machinery mechanistically unresolved
    • relationship to canonical surface ITGAV pool unclear
  16. 2025 High

    Further mechanisms diversified ITGAV's roles—autophagy regulation in cardiomyocytes, Notch trafficking in gastric cancer stemness, efferocytosis as an apoptotic-cell ligand, and context-dependent SMAD4 versus MAPK/ERK signaling—while a cell-type-specific knockout established that macrophage ITGAV is dispensable for post-infarction repair.

    Evidence Co-IP, trafficking and autophagy-flux assays, fibroblast/macrophage-specific KO mice, isogenic SMAD4+/- PDAC lines, and patient-derived models

    PMID:40555320 PMID:40736047 PMID:40739706 PMID:41318687 PMID:42056922

    Open questions at the time
    • unifying determinant of which downstream pathway ITGAV selects per context not defined
    • negative macrophage-MI result delimits but does not explain tissue-specific requirements

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single αV subunit's β-partner choice, ligand identity, and proteolytic processing (FURIN maturation versus γ-secretase ICD release) are coordinated to select among the many divergent downstream pathways attributed to ITGAV.
  • no structural model of the CD51-ICD or its cofactor complexes
  • determinants of β-subunit pairing across the documented functions not established
  • quantitative balance between membrane and nuclear ITGAV signaling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3 R-HSA-1643685 Disease 1
Partners
ADAM9FURINITGB3NR4A3NUMBPOSTNTGFBR1THBS1
Complex memberships
THBS1/ITGAV/TβRI complexαvβ1 integrinαvβ3 integrin

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 αvβ3 integrin (ITGAV/CD51 + β3) on melanoma cells directly binds human Thy-1 (CD90) expressed on activated endothelial cells, mediating melanoma cell adhesion and transmigration across the endothelium; this interaction was demonstrated by binding of purified Thy-1 to αvβ3-transfected cells and to purified αvβ3 integrin, and by blockade experiments under static and flow conditions. Purified protein binding assay, transfected cell adhesion assay, functional blocking antibody under static and flow conditions Oncogene Medium 15897908
2000 Coxsackievirus A9 binds integrin αvβ3 (CD51/CD61) at the CYDMKTTC sequence (residues 187–193) of the β3 subunit; importantly, an RGD-less CAV-9 mutant can still bind this site efficiently, demonstrating that RGD in the viral VP1 protein is not required for high-affinity interaction with αvβ3. Binding studies on CHO cells expressing αvβ3, αvβ1, or chimeric αvβ1-3-1 mutants; function-blocking monoclonal antibodies; competition with natural ligand vitronectin Human immunology Medium 10773347
1995 Human fetal liver-derived mast cells cultured with stem cell factor acquire functional CD51/CD61 (αvβ3) receptors and spontaneously adhere to vitronectin through this receptor; adhesion to fibronectin and laminin is partially inhibited by anti-CD61 and anti-CD29 antibodies, but no degranulation occurs during vitronectin-dependent adhesion. Flow cytometry, adhesion measurements, antibody-blocking assays, culture differentiation model Blood Medium 7542504
2016 ITGAV knockdown in human adipose-derived stem cells (ASCs) reduces proliferation, induces p21(Cip1), represses survivin, and specifically regulates the Hippo pathway mediator TAZ, while knockdown of either ITGAV or ITGA5 promotes adipogenic differentiation; transgenic ITGAV overexpression impairs adipogenesis, placing ITGAV as a negative regulator of adipogenic differentiation via RGD-motif signaling. siRNA knockdown, transgenic overexpression, cell proliferation assays, gene expression profiling, cilengitide pharmacological inhibition Scientific reports Medium 27363302
2016 Periostin (Postn) interacts with Itgav to regulate hematopoietic stem cell (HSC) proliferation via outside-in signaling; Itgav deletion in the hematopoietic system recapitulates peripheral blood phenotypes of Postn-knockout mice; mechanistically, the Postn-Itgav interaction inhibits the FAK/PI3K/AKT pathway in HSCs, increasing p27Kip1 expression and maintaining HSC quiescence. Conditional knockout mice (Vav-Cre), Postn-/- mice, HSC repopulation assays, in vitro proliferation, pathway analysis (FAK/PI3K/AKT/p27Kip1) Nature communications High 27905395
2017 ITGAV-containing integrin receptors on porcine trophoblast (pTr2) cells directly mediate adhesion to SPP1 (osteopontin); siRNA knockdown of ITGAV in pTr2 cells significantly reduces attachment to SPP1, and ITGAV, ITGB3 and SPP1 co-localize in large aggregates at the uterine luminal epithelium–trophoblast interface on Day 25 of gestation. siRNA knockdown, cell adhesion assay, in situ hybridization, immunofluorescence co-localization Reproduction (Cambridge, England) Medium 28250242
2016 CD51 (ITGAV) binds TGF-β receptors in colorectal cancer cells and upregulates TGF-β/Smad signaling; CD51+ CRC cells display enhanced sphere-forming, tumorigenic, migratory, invasive, and chemoresistance capacities compared to CD51- cells; CD51 knockdown reduces side population, sphere formation, motility, tumor incidence and metastasis in vivo. Co-immunoprecipitation (CD51–TGF-β receptor binding), siRNA knockdown, sphere-forming assay, in vivo tumor model Oncogene Medium 27593923
2019 Macrophage-expressed CD51 contributes to the acquisition of cancer stem cell (CSC) stemness traits in pancreatic cancer cells via the TGF-β1/Smad2/3 paracrine pathway; CD51 knockdown in macrophages drives them toward an M1-like phenotype and reduces CSC properties in co-cultured pancreatic cancer cells. siRNA knockdown in macrophages, co-culture assays, pathway analysis (TGF-β1/Smad2/3), phenotype characterization Cancer letters Medium 31199988
2020 TAZ (WWTR1), but not YAP, specifically drives ITGAV transcription in hepatocellular carcinoma cells; ITGAV promotes actin stress fiber assembly, tumor cell migration and invasion; perturbation of ITGAV diminishes actin fiber formation and reduces nuclear YAP/TAZ protein levels, establishing a positive feedback loop amplifying Hippo pathway activity. RNAi knockdown (TAZ, YAP, ITGAV), comprehensive expression profiling, actin staining, migration/invasion assays, nuclear fractionation Cancer letters Medium 31904487
2023 Runx2 transcriptionally activates Itgav expression by binding to its promoter in hepatic stellate cells (HSCs); Itgav is required downstream of Runx2 for HSC activation; blockade of Itgav attenuates Runx2-induced HSC activation and liver fibrosis in multiple mouse models; cytokines (TGF-β1, PDGF, EGF) promote Runx2 nuclear translocation via PKA. Runx2 ChIP-seq identifying ITGAV promoter binding, RNA-seq, siRNA/shRNA knockdown, HSC-specific in vivo overexpression/knockdown (HBAAV-Runx2, VA-Lip-Runx2), CCl4/DDC/MCD mouse models Clinical and translational medicine High 37403784
2024 CD51 undergoes transmembrane cleavage by γ-secretase to produce a functional intracellular domain (CD51-ICD); CD51-ICD facilitates HCC invasion and metastasis by promoting transcription of oxidative phosphorylation-related genes; cancer-associated fibroblast-derived periostin is the major driver of CD51 cleavage; combined inhibition of surface CD51 (cilengitide) and γ-secretase (LY3039478) shows enhanced therapeutic efficacy in patient-derived organoid and xenograft models. γ-secretase cleavage assay, nuclear ICD detection, RNA-seq for transcriptional targets, periostin-knockout transgenic mice, 3D invasion assay, patient-derived organoids and xenografts, bioluminescence imaging Journal of hepatology High 37604269
2023 CD51 (ITGAV) intracellular domain (ICD), generated by γ-secretase cleavage, binds transcription factor NR4A3 and acts as a co-activator to promote transcription of NTRK1, NTRK3, and SEMA3E, thereby promoting neurotropism and perineural invasion of colorectal cancer cells; pharmacological inhibition of γ-secretase impedes this process in vitro and in vivo. γ-secretase cleavage assay, co-immunoprecipitation (CD51-ICD/NR4A3), reporter assays, pharmacological γ-secretase inhibition in vitro and in vivo Cancers Medium 37174090
2018 p53 represses CD51 transcription via Sp1/Sp3 transcription factors in prostate cancer; loss of p53 function leads to elevated CD51 expression, and CD51 is required for prostate cancer stemness and metastasis properties. Reporter assays, ChIP, siRNA/overexpression, in vivo tumor models Cell death & disease Medium 29743605
2024 TGFβ type I receptor (TβRI) promotes CRPC cell migration and metastasis via production of thrombospondin 1 (THBS1), which mediates cell migration by interacting with ITGAV and TβRI; deletion of TβRI or THBS1 prevents cancer cell migration and invasion; this axis was confirmed in vivo in xenograft models. RNA-seq and proteomics of TGFβ-treated CRPC cells, CRISPR-Cas9 and siRNA knockdown of TβRI and THBS1, co-immunoprecipitation of THBS1/ITGAV/TβRI complex, in vivo xenograft assays Oncogene High 39304722
2024 ITGAV directly interacts with NET-DNA scaffolds in cholangiocarcinoma (CCA) cells; this interaction activates the NFκB signaling pathway, leading to upregulation of VEGF-A expression and promotion of CCA proliferation, migration, invasion, and angiogenesis; NET-DNA pull-down assay coupled with mass spectrometry identified ITGAV as the binding partner. NET-DNA pull-down + mass spectrometry, chromatin immunoprecipitation (ChIP), RNA sequencing, in vitro and in vivo (organoid and PAD4 KO mouse) models, ELISA Cell communication and signaling : CCS Medium 38326837
2025 Cytosolic ITGAV is a principal substrate of the proprotein convertase FURIN; FURIN-mediated maturation of ITGAV is required for lysosomal function and lipophagic flux in astrocytes; an ITGAV mutant that prevents FURIN cleavage diminishes lysosomal puncta and lipophagic processing, and mature (but not mutant) ITGAV rescues lipid droplet accumulation in FURIN-deficient cells. Immunoprecipitation-mass spectrometry (IP-MS), site-directed mutagenesis of FURIN cleavage site in ITGAV, lipophagic flux assays, lipidomics, FURIN-deficient mouse model Autophagy High 41376284
2022 ITGAV/αv integrin-dependent noncanonical autophagy is specifically induced in germinal center and memory B cell subpopulations in human tonsils and spleens; CRISPR-mediated knockdown of autophagy genes in human B cells shows that ITGAV/αv-dependent autophagy limits activation of specific B cell response pathways while promoting others, providing mechanistic links to immune dysregulation in lupus. CRISPR-mediated knockdown of autophagy genes, transcriptomic analysis, immunostaining of human tissue sections (tonsil, spleen), flow cytometry of B cell subsets Autophagy Medium 36016494
2024 Human biallelic loss-of-function ITGAV variants cause a previously unknown disease characterized by eye/brain abnormalities, inflammatory bowel disease, and immune dysregulation; mechanistically, reduced functional Integrin αV results in dysregulation of TGF-β-dependent signaling and αVβ3-regulated immune signaling; zebrafish itgav deletion recapitulates patient phenotypes including retinal/brain defects, loss of microglia, and colitis with reduced SMAD3 expression. Human genetics (biallelic variant identification), patient-derived cell functional studies, RNA sequencing, immunostaining, zebrafish itgav genetic deletion model The Journal of experimental medicine High 39526957
2025 In SMAD4-positive PDAC cells, ITGAV signals through the TGF-β/SMAD4 pathway to regulate proliferation, migration, and invasion; in SMAD4-negative PDAC cells, ITGAV influences only proliferation and migration via the MAPK/ERK pathway, demonstrating context-dependent SMAD4-dependent vs. SMAD4-independent downstream signaling. siRNA knockdown of ITGAV in isogenic SMAD4+ and SMAD4- PDAC cell lines, proliferation/migration/invasion assays, pathway analysis (SMAD4, MAPK/ERK) Molecular oncology Medium 40739706
2023 SOX11 binds the ITGAV gene promoter and transcriptionally regulates ITGAV expression in head and neck squamous cell carcinoma (HNSCC); SOX11 knockdown reduces ITGAV expression, and ITGAV knockdown inhibits migration, invasion, viability, and colony formation of HNSCC cells. Chromatin immunoprecipitation (ChIP) assay for SOX11 at ITGAV promoter, siRNA knockdown, cell functional assays Current oncology (Toronto, Ont.) Medium 38534932
2023 CASZ1 (transcription factor) binds the ITGAV promoter and transcriptionally regulates ITGAV expression in lung cancer cells; CASZ1 overexpression promotes lung cancer cell migration, invasion, and epithelial-mesenchymal transition through ITGAV, while CASZ1 knockdown suppresses these phenotypes and reduces metastasis in vivo. RNA-seq of CASZ1-silenced cells, ChIP assay for CASZ1 at ITGAV promoter, siRNA/overexpression, in vivo metastasis model American journal of cancer research Medium 36777515
2025 CCN1 secreted by cardiac fibroblasts binds ITGAV-ITGB1/integrin αvβ1 via its cysteine-knot-containing (CT) domain in cardiomyocytes, activating the PTK2/FAK-MTOR signaling pathway and inhibiting cardiomyocyte autophagy, thereby promoting diabetic cardiomyopathy; fibroblast-specific CCN1 knockout ameliorates cardiac dysfunction and restores autophagic activity in DCM mice. Proteomic analysis, co-immunoprecipitation (CCN1/ITGAV-ITGB1), molecular dynamics simulation, fibroblast-specific ccn1 knockout mouse, co-culture experiments, autophagy flux assays Autophagy High 42056922
2025 Macrophage ITGAV does not play a significant role in post-infarction cardiac repair and remodeling; myeloid cell-specific and macrophage-specific ITGAV knockout mice show no significant effects on macrophage recruitment, myofibroblast infiltration, collagen deposition, or angiogenesis after myocardial infarction; furthermore, fibronectin-induced changes in macrophage transcriptome (inflammatory, cell cycle, ECM proteolysis genes) are independent of ITGAV. Myeloid/macrophage-specific ITGAV knockout mice, scRNA-sequencing, immunofluorescence, in vitro RNA-sequencing of ITGAV-KO macrophages treated with fibronectin, cardiac function assessment Communications biology High 41318687
2010 Mast cell adhesion to bronchial smooth muscle (BSM) specifically depends on CD51 (ITGAV) and CD44 variant 6 (CD44v6); blockade of either CD51 or CD44 significantly decreases mast cell adhesion to BSM; adhesion is mediated primarily through type I collagen of the ECM; CD44v6 expression is increased in asthmatic BSM cells. 3H-thymidine-labeled mast cell adhesion assay, function-blocking antibodies, confocal immunofluorescence, electron microscopy, RT-PCR, western blot, flow cytometry Allergy Medium 20121756
2025 CD51 (ITGAV) promotes gastric cancer stemness by interacting with Numb, a negative regulator of Notch signaling, diverting Notch1 receptor trafficking from lysosomal degradation to plasma membrane recycling and thereby amplifying Notch pathway activation; pharmacological inhibition with cilengitide suppresses CSC phenotypes in vitro and in patient-derived organoids and xenografts. Co-immunoprecipitation (CD51/Numb), trafficking assays (lysosomal vs. plasma membrane recycling of Notch1), single-cell RNA sequencing, patient-derived organoids, xenograft models, siRNA/overexpression Cancer letters Medium 40555320
2025 ADAM9 in macrophages directly binds ITGAV on apoptotic polymorphonuclear leukocytes (PMNs); inhibiting ITGAV expression on PMNs improves ADAM9-mediated macrophage efferocytosis; blocking the ADAM9/ITGAV interaction ameliorates sepsis-induced acute lung injury by promoting macrophage clearance of apoptotic neutrophils. Co-immunoprecipitation (ADAM9/ITGAV), siRNA knockdown of ITGAV, in vitro efferocytosis assay, LPS-induced ALI mouse model FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 40736047
2024 Activation of IGF1R signaling in epithelial cutaneous squamous cell carcinoma (cSCC) cells is necessary to induce epithelial-mesenchymal plasticity (EMP) and promotes ITGAV expression; ITGAV knockdown in epithelial plastic cancer cells blocks EMP acquisition, generating epithelial tumors; ITGAV collaborates with IGF1R to drive cSCC progression. Genetic knockdown (ITGAV siRNA), pharmacological IGF1R inhibition, mouse cSCC progression model, phosphoproteomic analysis, flow cytometry, immunofluorescence Journal of experimental & clinical cancer research : CR Medium 39075581
2018 Demethylation of the ITGAV gene promoter in response to blast-induced shock wave accelerates osteogenic differentiation and mineral deposition in human mesenchymal cells; pharmacological targeting of ITGAV abrogates shock wave-induced mineralization, demonstrating that epigenetic upregulation of ITGAV is required for this process. Reduced representation bisulfite sequencing (DNA methylation), osteogenic differentiation assays, pharmacological ITGAV inhibition (cilengitide), mineral deposition quantification Bone Medium 30219480
2025 LGALS3BP induces ITGAV expression in hepatocellular carcinoma cells by enhancing JunB (JUNB) transcriptional activity; ChIP assays confirmed JunB binding at ITGAV promoter sites; LGALS3BP knockdown suppresses ITGAV expression and reduces cell-to-cell adhesion and invasiveness. ChIP assay (JunB at ITGAV promoter), recombinant LGALS3BP treatment, siRNA knockdown, qRT-PCR, western blot, cell adhesion and invasion assays Anticancer research Medium 40578967
1993 CD51 (ITGAV) is expressed on the basal surface of myoepithelial cells at the myoepithelial-stromal junction in normal breast tissue and co-distributes with TSP1 in invasive lobular carcinoma cells, suggesting a functional receptor-ligand relationship between TSP1 and CD51 at these sites. Immunohistochemistry, in situ hybridization Cancer research Low 7680285
2000 The ITGAV gene encodes a 150-kDa mature peptide from a 3,146-bp coding sequence; gene structure characterization revealed the genomic organization enabling mechanistic studies of this integrin subunit. Gene cloning, cDNA characterization, genomic sequencing Cytogenetics and cell genetics Low 10965141
1993 The human ITGAV gene (vitronectin receptor alpha subunit, VNRA) was regionally mapped to chromosome 2q31→q32 by fluorescence in situ hybridization. Fluorescence in situ hybridization (FISH) with GTG-banding on human-rodent somatic cell hybrids Cytogenetics and cell genetics Low 7678549

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. The Journal of experimental medicine 413 23776077
1993 Expression of thrombospondin (TSP1) and its receptors (CD36 and CD51) in normal, hyperplastic, and neoplastic human breast. Cancer research 142 7680285
2016 ITGAV and ITGA5 diversely regulate proliferation and adipogenic differentiation of human adipose derived stem cells. Scientific reports 98 27363302
2005 Interaction of human Thy-1 (CD 90) with the integrin alphavbeta3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium. Oncogene 79 15897908
2016 Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis. Nature communications 69 27905395
2019 LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics 65 31285770
2020 ITGAV targeting as a therapeutic approach for treatment of metastatic breast cancer. American journal of cancer research 60 32064162
2012 Relationship between the expression of the extracellular matrix genes SPARC, SPP1, FN1, ITGA5 and ITGAV and clinicopathological parameters of tumor progression and colorectal cancer dissemination. Oncology 60 23128103
2019 Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. Cancer letters 58 31199988
2017 Transplantation of CD51+ Stem Leydig Cells: A New Strategy for the Treatment of Testosterone Deficiency. Stem cells (Dayton, Ohio) 56 28090714
2017 ITGAV (alpha v integrins) bind SPP1 (osteopontin) to support trophoblast cell adhesion. Reproduction (Cambridge, England) 53 28250242
2014 Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer. Anticancer research 52 25275062
2017 miR-217-5p induces apoptosis by directly targeting PRKCI, BAG3, ITGAV and MAPK1 in colorectal cancer cells. Journal of cell communication and signaling 49 28905214
2017 Elevation of MiR-9-3p suppresses the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via down-regulating FN1, ITGB1 and ITGAV. Cancer biology & therapy 46 28613134
2020 TAZ target gene ITGAV regulates invasion and feeds back positively on YAP and TAZ in liver cancer cells. Cancer letters 45 31904487
2016 CD51 correlates with the TGF-beta pathway and is a functional marker for colorectal cancer stem cells. Oncogene 44 27593923
2010 Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6. Allergy 41 20121756
1995 Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin. Blood 37 7542504
1997 Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression. Journal of cardiovascular pharmacology 36 9007665
2023 Runx2 activates hepatic stellate cells to promote liver fibrosis via transcriptionally regulating Itgav expression. Clinical and translational medicine 34 37403784
2007 Chicken thrombocytes express the CD51/CD61 integrin. Veterinary immunology and immunopathology 32 17659354
2020 Integrin alpha V (ITGAV) expression in esophageal adenocarcinoma is associated with shortened overall-survival. Scientific reports 31 33110104
2009 Mevinolin enhances osteogenic genes (ALP, type I collagen and osteocalcin), CD44, CD47 and CD51 expression during osteogenic differentiation. Life sciences 30 19162043
2016 Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer. International journal of oncology 29 26846197
2018 p53-dependent CD51 expression contributes to characteristics of cancer stem cells in prostate cancer. Cell death & disease 27 29743605
2000 High affinity interactions of Coxsackievirus A9 with integrin alphavbeta3 (CD51/61) require the CYDMKTTC sequence of beta3, but do not require the RGD sequence of the CAV-9 VP1 protein. Human immunology 27 10773347
2020 Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis. Frontiers in genetics 26 32351538
2016 Decreased Expression of miR-548c-3p in Osteosarcoma Contributes to Cell Proliferation Via Targeting ITGAV. Cancer biotherapy & radiopharmaceuticals 25 27310302
2024 The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB. Cell communication and signaling : CCS 23 38326837
2018 Inhibition of skin carcinogenesis by suppression of NF-κB dependent ITGAV and TIMP-1 expression in IL-32γ overexpressed condition. Journal of experimental & clinical cancer research : CR 23 30486830
2019 IL-32γ suppresses lung cancer stem cell growth via inhibition of ITGAV-mediated STAT5 pathway. Cell death & disease 21 31263095
2020 LncRNA KCNQ1OT1 knockdown inhibits viability, migration and epithelial-mesenchymal transition in human lens epithelial cells via miR-26a-5p/ITGAV/TGF-beta/Smad3 axis. Experimental eye research 20 32950535
2007 The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study. Arthritis research & therapy 19 17615072
2023 Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma. Journal of hepatology 18 37604269
2014 CD14+ CD16+ monocytes rather than CD14+ CD51/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study. International journal of laboratory hematology 17 24661393
1994 Localization of thrombospondin, CD36 and CD51 during prenatal development of the human mammary gland. Differentiation; research in biological diversity 17 7520877
2023 Chronological and Replicative Aging of CD51+/PDGFR-α+ Pulp Stromal Cells. Journal of dental research 16 36919905
2019 CD51 distinguishes a subpopulation of bone marrow mesenchymal stem cells with distinct migratory potential: a novel cell-based strategy to treat acute myocardial infarction in mice. Stem cell research & therapy 16 31747966
2018 Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model. Bone 15 30219480
2017 Expression of PGR, HBEGF, ITGAV, ITGB3 and SPP1 genes in eutopic endometrium of infertile women with endometriosis during the implantation window: a pilot study. JBRA assisted reproduction 15 28837027
2009 The ITGAV rs3738919 variant and susceptibility to rheumatoid arthritis in four Caucasian sample sets. Arthritis research & therapy 13 19818132
2000 Cloning and characterisation of ITGAV, the genomic sequence for human cell adhesion protein (vitronectin) receptor alpha subunit, CD51. Cytogenetics and cell genetics 13 10965141
2022 Transcriptomic analysis of pathways associated with ITGAV/alpha(v) integrin-dependent autophagy in human B cells. Autophagy 12 36016494
2020 Notoginsenoside R1 Protects Against the Acrylamide-Induced Neurotoxicity via Upregulating Trx-1-Mediated ITGAV Expression: Involvement of Autophagy. Frontiers in pharmacology 12 32982756
2017 miR-25 Mediates Retinal Degeneration Via Inhibiting ITGAV and PEDF in Rat. Current molecular medicine 12 29210651
2024 The TβRI promotes migration and metastasis through thrombospondin 1 and ITGAV in prostate cancer cells. Oncogene 11 39304722
2019 Ilex hainanensis Merr targets ITGAV to suppress the proliferation and metastasis of osteosarcoma cells. OncoTargets and therapy 11 31239718
2007 Association of ITGAV supports a role of angiogenesis in rheumatoid arthritis. Arthritis research & therapy 11 18001496
2022 Circular RNA hsa_circ_0051040 Promotes Hepatocellular Carcinoma Progression by Sponging miR-569 and Regulating ITGAV Expression. Cells 10 36429000
2021 Cardiac Derived CD51-Positive Mesenchymal Stem Cells Enhance the Cardiac Repair Through SCF-Mediated Angiogenesis in Mice With Myocardial Infarction. Frontiers in cell and developmental biology 10 33968928
2006 Activated osteoclasts with CD51/61 expression in otosclerosis. The Laryngoscope 10 16885757
2024 Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis. The Journal of experimental medicine 9 39526957
2022 Exome Sequencing Identifies the Extremely Rare ITGAV and FN1 Variants in Early Onset Inflammatory Bowel Disease Patients. Frontiers in pediatrics 9 35692981
2021 MiR-197 Inhibitor Loaded AbCD133@MSNs@GNR Affects the Development of Prostate Cancer Through Targeting ITGAV. Frontiers in cell and developmental biology 9 34195187
1993 Regional localization of the human vitronectin receptor alpha subunit gene (VNRA) to chromosome 2q31-->q32. Cytogenetics and cell genetics 9 7678549
2024 ITGAV Promotes the Progression of Head and Neck Squamous Cell Carcinoma. Current oncology (Toronto, Ont.) 8 38534932
2023 CASZ1 promotes migration, invasion, and metastasis of lung cancer cells by controlling expression of ITGAV. American journal of cancer research 8 36777515
2025 3D pancreatic ductal adenocarcinoma desmoplastic model: Glycolysis facilitating stemness via ITGAV-PI3K-AKT-YAP1. Biomaterials advances 7 39889369
2004 Quantitation and kinetics of CD51 surface receptor expression: implications for targeted delivery. Annals of biomedical engineering 7 15171619
2023 CD51 Intracellular Domain Promotes Cancer Cell Neurotropism through Interacting with Transcription Factor NR4A3 in Colorectal Cancer. Cancers 6 37174090
2022 WDHD1 is over-expressed in nasopharyngeal carcinoma and may control the expression of ITGAV. FEBS open bio 6 36345604
2014 The ITGAV-rs3911238 polymorphism is associated with disease activity in rheumatoid arthritis. Iranian journal of allergy, asthma, and immunology 6 25150077
2010 Lack of association between markers in the ITGA3, ITGAV, ITGA6 and ITGB3 and autism in an Irish sample. Autism research : official journal of the International Society for Autism Research 6 21182210
1997 Could coenzyme Q10 affect hemostasis by inhibiting platelet vitronectin (CD51/CD61) receptor? Molecular aspects of medicine 6 9266521
2024 IGF1R signaling induces epithelial-mesenchymal plasticity via ITGAV in cutaneous carcinoma. Journal of experimental & clinical cancer research : CR 5 39075581
2023 miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV. Pathobiology : journal of immunopathology, molecular and cellular biology 5 36724751
2011 Two cDNAs coding for the porcine CD51 (αv) integrin subunit: cloning, expression analysis, adhesion assays and chromosomal localization. Gene 5 21549183
2021 MiR-139 inhibits proliferation, migration and invasion of osteosarcoma cell line MG63 via down-regulating integrin subunit alpha V(ITGAV). Tissue & cell 4 35007826
2024 Relationship between aggressive features of oral squamous cell carcinoma and the immunoexpression of CX3CR1, CX3CL1 and ITGAV. Oral surgery, oral medicine, oral pathology and oral radiology 3 38760287
2024 Zuogui Wan modulates macrophage polarization and promotes osteogenic differentiation through regulation of CD51-positive bone marrow mesenchymal stem cells. Scientific reports 3 39478130
2023 Expression and function of CD51 on CD8 T cells as an immunomodulatory target. Biochemical and biophysical research communications 3 37087799
2021 CD271+CD51+PALLADIN- Human Mesenchymal Stromal Cells Possess Enhanced Ossicle-Forming Potential. Stem cells and development 3 33926240
2013 The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis. Rheumatology international 3 24375314
2025 CD51 promotes gastric cancer stemness via blocking Numb-mediated Notch1 degradation. Cancer letters 2 40555320
2025 Blocking the ADAM9/ITGAV Pathway Ameliorates Sepsis-Induced Acute Lung Injury by Promoting Macrophage Efferocytosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 40736047
2025 Cerebral FURIN deficiency impairs astrocytic lipophagy through ITGAV maturation. Autophagy 2 41376284
2024 Effect of heat exposure on prostaglandin production and expression of COX-2, PGES, PGFS, ITGAV and LGALS15 mRNAs in endometrial epithelial cells of buffalo (Bubalus bubalis). Molecular biology reports 2 38457014
2020 Association of ITGAV polymorphisms and risk of rheumatoid arthritis: evidence from a meta-analysis. Expert review of clinical immunology 2 32476506
2018 A Synonymous Mutation at Bovine Alpha Vitronectin Domain of Integrin Host Receptor (ITGAV) Gene Effect the Susceptibility of Foot-and-Mouth Disease in Crossbred Cattle. Advances in experimental medicine and biology 2 28567614
1991 Confirmation of the assignment of the vitronectin (VNRA) and fibronectin (FNRA) receptor alpha-subunits. Annals of human genetics 2 1722386
2025 Dicer inhibition delays wound closure by increasing Suz12 levels and regulating ITGAV levels in keratinocytes. Journal of molecular endocrinology 1 39807696
2025 ITGAV, a specific biomarker associated with the pathogenesis of idiopathic pulmonary fibrosis. Scientific reports 1 40374686
2025 ITGAV and SMAD4 influence the progression and clinical outcome of pancreatic ductal adenocarcinoma. Molecular oncology 1 40739706
2025 Pan-cancer landscape of ITGAV and its potential role in gastric cancer. Scientific reports 1 40775431
2025 Macrophage ITGAV is dispensable for post-infarction remodeling in mice and does not mediate fibronectin responses. Communications biology 1 41318687
2021 Exploring Single Nucleotide Polymorphisms in ITGAV for Gastric, Pancreatic and Liver Malignancies: An Approach Towards the Discovery of Biomarker. Combinatorial chemistry & high throughput screening 1 32819225
2026 Pathogenic mechanism of Eimeria tenella EtMIC2 promotes Eimeria tenella invasion and inhibits host cell apoptosis through binding to the ITGAV receptor. Poultry science 0 42025007
2026 Cardiac fibroblast-derived CCN1 aggravates diabetic cardiomyopathy through ITGAV-ITGB1/integrin αvβ1-mediated autophagy inhibition. Autophagy 0 42056922
2026 MicroRNA-563 as a potential biomarker in triple-negative breast cancer: impeding tumor progression by targeting ITGAV and epithelial-mesenchymal transition. World journal of surgical oncology 0 42169120
2026 Individual Variations in Anti-αvβ6 Autoantibody Levels Determined by ITGAV Gene Polymorphisms: Associations with Genetic Background and Relapse in Ulcerative Colitis. Inflammatory intestinal diseases 0 42222526
2026 CD44, CDH6, ITGAV, and SERPINE1 are Epithelial‒Mesenchymal Transition Markers in Gastric Cancer. Current medicinal chemistry 0 42227526
2026 Downregulation of miR-10b-3p by EBV promotes tumor growth and metastasis via ITGAV in nasopharyngeal carcinoma. PLoS pathogens 0 42263107
2025 Effect of fibrin on the expression of adhesion molecules (ICAM-1, ITGAV, and ITGB3) in unrestricted somatic stem cells. Hematology, transfusion and cell therapy 0 40315755
2025 ITGAV Regulation of LGALS3BP-JUNB Axis Facilitates the Cell-to-Cell Adhesion and Invasiveness of Hepatic Cancer Cells. Anticancer research 0 40578967
2025 Elevated ITGAV Expression in Seropositive Rheumatoid Arthritis: Diagnostic Potential and Immunopathological Insights. Journal of inflammation research 0 41287769
2023 Thiol-Based Modification of MarR Protein VnrR Regulates Resistance Toward Nitrofuran in Vibrio cholerae By Promoting the Expression of a Novel Nitroreductase VnrA and of NO-Detoxifying Enzyme HmpA. Antioxidants & redox signaling 0 37742113

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