Affinage

ITGA6

Integrin alpha-6 · UniProt P23229

Length
1130 aa
Mass
126.6 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 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

ITGA6 encodes the α6 integrin subunit, a laminin receptor that pairs with β1 (α6β1/VLA-6) or β4 (α6β4) to mediate cell adhesion, migration, and signaling across hematopoietic, epithelial, and stem cell lineages (PMID:2973567, PMID:2967289, PMID:1698797). The α6 subunit is a disulfide-linked heavy/light chain protein subject to variable N-glycosylation and proteolytic cleavage, and a substantial pool of β4 exists at the cell surface independent of α6 (PMID:1698797). α6β1 functions as the dominant laminin receptor on platelets, neutrophils, T cells, and mast cells, where it supports cation-dependent adhesion (Mn2+/Co2+/Mg2+ but not Ca2+), tethering and arrest under shear flow, and CD18-independent leukocyte migration, and provides costimulatory signals to T-cell proliferation (PMID:2973567, PMID:1972721, PMID:1347710, PMID:10698619). Distinct epitopes of α6 separate its adhesion and migration functions, the latter being required for melanoma movement on laminin and in vivo extravasation (PMID:9288792); the receptor associates laterally with the tetraspanin CD63 in selective integrin complexes (PMID:7629079). Upon laminin engagement and cooperation with β1, α6 activates PI3K/AKT signaling that suppresses p53 to sustain stem cell self-renewal and pluripotency, and drives invasion, EMT, and metastasis via IGF1R/Snail and related axes in cancer (PMID:22311737, PMID:38658801, PMID:24317509). ITGA6 expression is heavily controlled at multiple levels: transcriptionally by activators (HIF, RUNX1, RFX1, YB-1, MYC, TRIM28) and repressors (NFAT1, KLF9/SIN3A) (PMID:20332234, PMID:27001172, PMID:28926098, PMID:27228460, PMID:34497119, PMID:34968869), post-transcriptionally by m6A modification written by METTL3/ZC3H13 and read by YTHDF1/YTHDF3 to promote translation and mRNA stability (PMID:31409574, PMID:38670474, PMID:37003532), and post-translationally by FUT8-mediated core fucosylation that protects α6 from TRIM21-directed ubiquitination and degradation (PMID:38523237). RFX1-dependent Itga6 expression is required for testis cord integrity, establishing a non-malignant developmental role (PMID:27228460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1988 High

    Established that the α6 subunit constitutes a specific laminin receptor distinct from other VLA integrins, defining the molecular identity and ligand specificity of ITGA6.

    Evidence Antibody blocking of platelet adhesion to ECM proteins with cation substitution; sequential immunodepletion, V8 peptide mapping and 2D gels distinguishing α5 from α6

    PMID:2967289 PMID:2973567

    Open questions at the time
    • Did not resolve the binding interface on laminin
    • β-subunit pairing rules not yet defined
  2. 1990 High

    Resolved that α6 forms two alternative heterodimers (α6β1 and α6β4) with distinct biochemistry, defining the combinatorial receptor architecture.

    Evidence Sequential immunoprecipitation with anti-β4 depletion, SDS-PAGE, and immunoperoxidase tissue staining

    PMID:1698797

    Open questions at the time
    • Functional difference between α6β1 and α6β4 signaling not addressed
    • Regulation of pairing choice unknown
  3. 1990 Medium

    Extended α6β1 function from passive adhesion to active immune signaling, showing VLA-6/laminin provides costimulation to T-cell proliferation.

    Evidence Antibody blocking with co-immobilized CD3 mAb and laminin in human CD4+ T cells, flow cytometry

    PMID:1972721

    Open questions at the time
    • Intracellular signaling mediators of costimulation not defined
    • Single-lab antibody-based readout
  4. 1992 High

    Demonstrated α6β1 mediates CD11/CD18-independent leukocyte adherence to laminin, broadening its role in innate immune trafficking.

    Evidence Anti-α6 antibody blockade with CD11/CD18-deficient neutrophils as genetic confirmation

    PMID:1347710

    Open questions at the time
    • Downstream activation pathway in neutrophils not mapped
  5. 1995 High

    Identified a lateral partner (CD63) and a hypoxia-linked signaling output, placing α6β1 within tetraspanin-organized membrane complexes and inside-out activation contexts.

    Evidence Brij-96 co-IP, large-scale purification and N-terminal sequencing for CD63; antibody cross-linking with pharmacological inhibitors for hypoxic CD11b/CD18 upregulation

    PMID:7541723 PMID:7594504 PMID:7629079

    Open questions at the time
    • Functional consequence of CD63 association not established
    • Direct interaction site within the integrin complex unmapped
  6. 1997 High

    Separated adhesion from migration functions of α6, showing a distinct epitope drives motility and in vivo extravasation independent of FAK phosphorylation.

    Evidence Two anti-α6 antibodies with differential effects in laminin migration assays and in vivo B16F1 liver extravasation videomicroscopy

    PMID:9288792

    Open questions at the time
    • Molecular signaling distinguishing the migration epitope unknown
    • Mechanism uncoupled from FAK not explained
  7. 2000 Medium

    Established α6β1 functions under physiological shear, mediating leukocyte tethering and arrest on laminin with chain-specific selectivity.

    Evidence Defined laminar shear flow adhesion assay with chain-specific blocking antibodies

    PMID:10698619

    Open questions at the time
    • Force-dependent conformational regulation not addressed
    • Single-lab study
  8. 2012 Medium

    Connected α6 to stem cell maintenance, showing it acts downstream of OCT4/SOX2 and drives PI3K/AKT activation that suppresses p53 to sustain pluripotency.

    Evidence ChIP for OCT4/SOX2 at ITGA6 promoter, knockdown/overexpression with p-AKT and p53 readouts, sphere formation; double knockdown with ITGB1 in CSC migration

    PMID:22311737 PMID:24317509

    Open questions at the time
    • Direct link between α6 engagement and PI3K recruitment not biochemically resolved
    • Single-lab pathway data
  9. 2016 High

    Defined a transcriptional regulatory network controlling ITGA6, identifying activators (HIF, RUNX1, RFX1) and linking expression to invasion and tissue integrity.

    Evidence ChIP plus luciferase reporters with epistatic rescue (HIF), motif mutagenesis (RUNX1), and conditional Rfx1 knockout with testis cord phenotype

    PMID:27001172 PMID:27228460 PMID:28926098

    Open questions at the time
    • Combinatorial logic among transcription factors unresolved
    • Cell-type specificity of each regulator not systematized
  10. 2019 High

    Established multilayered post-transcriptional control via m6A, showing METTL3-deposited methylation read by YTHDF1/YTHDF3 promotes ITGA6 mRNA translation and tumor cell invasion, reversibly opposed by ALKBH5.

    Evidence MeRIP, RIP, luciferase + m6A-site mutagenesis, METTL3/ALKBH5 perturbation, and epistatic rescue with xenografts

    PMID:31409574

    Open questions at the time
    • Relative contribution of translation vs stability not fully partitioned
    • Reader selectivity mechanism unresolved
  11. 2021 Medium

    Expanded the regulatory map with additional transcriptional, epigenetic, and physical-interaction inputs (TRIM28, SIN3A/KLF9, KDM5B/miR-448, PSMC2) tying ITGA6 to cancer stemness and progression.

    Evidence Co-IP, ChIP, miRNA luciferase targeting, genetic inactivation, and epistasis with in vivo metastasis models

    PMID:33829656 PMID:34413286 PMID:34497119 PMID:34968869

    Open questions at the time
    • Many interactions rest on single Co-IP without reciprocal validation
    • Convergence of these inputs on a shared output not integrated
  12. 2024 High

    Defined post-translational stabilization of α6 through FUT8 core fucosylation, which blocks TRIM21-mediated ubiquitination, sustaining PI3K/AKT signaling and adult neurogenesis.

    Evidence Co-IP, core fucosylation biochemistry, Fut8 conditional knockout, ubiquitination assay, Trim21 co-IP, and Akt-agonist rescue

    PMID:38523237

    Open questions at the time
    • Fucosylation site mapping on α6 not detailed
    • Generalizability beyond neural stem cells untested
  13. 2024 Medium

    Linked α6 engagement to a feed-forward IGF1R/Snail loop driving EMT, chemoresistance, and pre-metastatic niche formation, and to additional m6A stabilization in non-malignant airway disease.

    Evidence Isogenic platinum-resistant ovarian models with genetic/pharmacological perturbation and xenografts; MeRIP-PCR and actinomycin D stability assays for ZC3H13 in COPD models

    PMID:38658801 PMID:38670474

    Open questions at the time
    • Direct biochemical coupling of α6 to IGF production not resolved
    • Single-lab models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct β1 vs β4 heterodimers, lateral partners, and the dense transcriptional/m6A/fucosylation regulatory layers are coordinated to specify adhesion versus migration versus stemness outputs in a given cell remains unresolved.
  • No structural model of α6 ligand engagement in the corpus
  • Integration of the multiple regulatory inputs into a unified signaling logic not established
  • In vivo isoform-specific functions of α6β1 vs α6β4 not dissected

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
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
CD63FUT8ITGB1ITGB4PSMC2RPSATRIM21TRIM28
Complex memberships
α6β1 integrin (VLA-6)α6β4 integrin

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 ITGA6 (VLA-6, α6β1 integrin) functions as a laminin receptor on platelets. Antibody blockade of the α6 subunit specifically inhibited platelet adhesion to laminin but not to fibrinogen, fibronectin, or collagen. Adhesion was supported by Mn2+, Co2+, and Mg2+ but not Ca2+, Zn2+, or Cu2+. Monoclonal antibody blocking assay, platelet adhesion assay with extracellular matrix proteins, cation substitution experiments Nature High 2973567
1988 VLA-6 is a distinct heterodimer on platelets (α6β1) separate from VLA-2 and VLA-5, identified biochemically. The α6 subunit is only loosely or partially associated with the common VLA β subunit, and α5 and α6 subunits have distinct V8 peptide maps and 2D gel migration patterns. Sequential immunodepletion, V8 protease peptide mapping, 2D O'Farrell gel electrophoresis, anti-α5 and anti-α6 antibody immunoprecipitation The Journal of biological chemistry High 2967289
1990 ITGA6 forms two distinct integrin complexes: α6β1 (VLA-6) and α6β4. Monoclonal antibodies against β4 preclear α6β4 but not α6β1 from cell extracts. A substantial fraction of β4 at the cell surface is not associated with α6. The α6 subunit consists of disulfide-linked heavy and light chains with variability in N-linked glycan modification and differential proteolytic cleavage. Sequential immunoprecipitation, SDS-PAGE, immunoperoxidase staining of tissue sections, anti-β4 monoclonal antibody depletion assays Journal of cell science High 1698797
1990 VLA-6/laminin interaction provides costimulatory signaling to CD3-mediated T cell proliferation. Antibody blockade of the α6 subunit specifically inhibited VLA-6/laminin-dependent costimulation of resting human CD4+ T cells. T cell activation (CD3/TCR crosslinking or PMA) induces rapid but transient VLA-6 binding function; memory T cells express higher VLA-6 than naive T cells. Monoclonal antibody blocking assay, T cell proliferation assay with co-immobilized CD3 mAb and laminin, flow cytometry Journal of immunology Medium 1972721
1992 CD11/CD18-independent neutrophil (PMN) adherence to laminin is mediated specifically by VLA-6 (α6β1). Anti-α6 antibodies (GoH3 and 450-30) significantly reduced phorbol myristate acetate-stimulated PMN adherence to laminin when CD11/CD18 was blocked, and GoH3 completely inhibited adherence of CD11/CD18-deficient PMNs to laminin. Monoclonal antibody blocking assay, PMN adhesion assay to laminin-coated surfaces, flow cytometry for VLA-6 expression on PMN Blood High 1347710
1995 CD63 specifically associates with α6β1 (VLA-6) and α3β1 integrins but not α2β1 or α5β1. Large-scale purification using an antibody to the integrin-associated protein yielded CD63. The cytoplasmic domain of α3 was neither required nor sufficient for CD63 association, suggesting the interaction occurs elsewhere in the complex. Brij 96 detergent co-immunoprecipitation, large-scale purification and N-terminal sequencing, colocalization by immunofluorescence, domain deletion analysis The Journal of biological chemistry High 7629079
1997 VLA-6 (α6β1) plays an active role in cell migration on laminin beyond initial adhesion. Antibody MA6, which does not inhibit VLA-6-mediated adhesion, still blocked melanoma cell movement on laminin and inhibited in vivo extravasation in liver, without affecting tyrosine phosphorylation of focal adhesion kinase. This demonstrates a distinct epitope on α6 involved in migration but not adhesion. Cell migration assay on laminin, in vivo videomicroscopy of B16F1 extravasation in liver, FAK phosphorylation assay, two different anti-α6 antibodies with distinct functional effects Cancer research High 9288792
1995 VLA-5 and VLA-6 together mediate CD18-independent PMNL migration through synovial fibroblast barriers in response to chemotactic factors. Combined blockade of α5 (VLA-5) plus α6 (VLA-6) was required to inhibit CD18-independent migration to the same degree as anti-β1 integrin antibody alone. Monoclonal antibody blocking assay, PMNL migration through fibroblast barrier on microporous filters, chemotactic gradient assay Cellular immunology Medium 7541723
1995 During hypoxia, integrin signaling via α6β1 (VLA-6) engagement on PMNs results in upregulation of CD11b/CD18 expression, dependent on intracellular Ca2+, GPLC activity, and protein tyrosine kinase activity. Cross-linking VLA-6 in fluid-phase PMN progressively increased CD11b/CD18 expression during hypoxia but not normoxia. Anti-VLA-6 antibody blocking and cross-linking, pharmacological inhibition (genistein, herbimycin A, U73122, cyclopiazonic acid), Ca2+ depletion/restoration, flow cytometry Journal of immunology Medium 7594504
1996 VLA-6 (α6β1) integrin is expressed and utilized by mouse bone marrow-derived mast cells (BMMC) to adhere to laminin. Using two α6-specific antibodies (MA6 and GoH3), VLA-6 was identified as the laminin receptor on BMMC and long-term mast cell lines. Mast cell adhesion assay to multiple laminin substrates, flow cytometry, two distinct anti-α6 antibodies (MA6 and GoH3) Allergy Medium 8899118
2000 α6β1 integrin (VLA-6) mediates leukocyte tethering and arrest on laminin under physiological shear flow. Antibodies to both α6 and β1 chains abrogated PMN tethering to laminin but not to fibronectin or vitronectin. Antibodies to α2, α3, and β4 showed no significant inhibition, demonstrating specificity of α6β1. Flow adhesion assay under defined laminar shear flow, monoclonal antibody blocking with chain-specific antibodies Cellular immunology Medium 10698619
2010 Y-box binding protein-1 (YB-1) directly binds the CD49f (ITGA6) promoter and transcriptionally upregulates its expression. Introduction of wild-type or activated YB-1 stimulated CD49f production; silencing YB-1 decreased CD49f expression and reporter activity. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA knockdown, YB-1 overexpression, flow cytometry Cancer research Medium 20332234
2012 CD49f (ITGA6) activates PI3K/AKT signaling and suppresses p53, regulating differentiation and pluripotency of mesenchymal stem cells. Forced CD49f expression prolonged PI3K/AKT activation; knockdown in hESCs downregulated PI3K/AKT and upregulated p53, inducing differentiation. OCT4 and SOX2 were found to be recruited to the putative ITGA6 promoter region, placing ITGA6 downstream of pluripotency factors. ChIP for OCT4/SOX2 at ITGA6 promoter, siRNA knockdown, overexpression, western blot for p-AKT and p53, sphere formation assay Stem cells Medium 22311737
2016 ITGA6 is a direct transcriptional target of hypoxia-inducible factors (HIFs). HIF binding to ITGA6 regulatory elements was verified by chromatin immunoprecipitation and luciferase reporter assays. ITGA6 knockdown significantly reduced invasion, and re-expression of ITGA6 in HIF-knockdown cells partially rescued the invasion phenotype. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA knockdown, FACS sorting, invasion assay, HIF KO mouse model Molecular cancer High 27001172
2016 RUNX1 binds to and activates the ITGA6 promoter through a consensus RUNX1 binding motif in myeloid cells, regulating ITGA6 expression. This regulation is distinct from RUNX1's regulation of ITGB4, where RUNX1 activates the ITGB4 promoter without a recognized consensus binding motif. Chromatin immunoprecipitation (ChIP), promoter-reporter assays, site-directed mutagenesis of RUNX1 binding motif Journal of cellular physiology Medium 28926098
2016 RFX1 directly activates transcription of Itga6 in Sertoli cells and is required for testis cord integrity. Luciferase and ChIP assays confirmed direct RFX1 binding to the Itga6 promoter. Conditional Rfx1 knockout mice had disrupted testis cords and significantly decreased integrin α6 expression. Conditional Rfx1 knockout mice (Rfx1flox/flox; Amh-Cre), luciferase reporter assay, chromatin immunoprecipitation (ChIP), immunofluorescence Molecular reproduction and development High 27228460
2017 Oncogenic K-RasV12 upregulates ITGA6 expression via the MAPK/ERK/FOSL1 signaling cascade in MDCK cells, promoting anoikis resistance and metastatic capacity. Re-expression of αV-integrin in K-RasV12-transformed cells synergistically upregulated ZEB1 and TWIST1 and triggered EMT. K-RasV12 expression in MDCK cells, siRNA knockdown, transcriptomic analysis, FOSL1 pathway inhibition, anoikis resistance assay, cyst growth assay Oncogene Medium 28604746
2018 MYC regulates ITGA6 promoter activity and alternative splicing to favor the pro-proliferative ITGA6A variant in colorectal cancer cells. MYC inhibition or knockdown decreased ITGA6 and ITGA6A levels and reduced the splicing factor ESRP2; ChIP revealed MYC occupancy at both ITGA6 and ESRP2 proximal promoters. ChIP, luciferase reporter assay, pharmacological MYC inhibitor (10058-F4), shRNA knockdown, RT-PCR for splice variants Cancers Medium 29401653
2019 METTL3-mediated m6A methylation of ITGA6 mRNA 3'UTR promotes its translation via binding of m6A readers YTHDF1 and YTHDF3 in bladder cancer cells. The eraser ALKBH5 reverses this effect. Overexpression of ITGA6 in METTL3-depleted cells partially restored bladder cancer cell adhesion, migration, and invasion. Methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), luciferase reporter assay, mutagenesis of m6A sites, METTL3/ALKBH5 knockdown/overexpression, xenograft mouse model EBioMedicine High 31409574
2019 ITGA6 interacts with ribosomal protein SA (RPSA) in pancreatic cancer cells, identified by Co-IP combined with mass spectrometry. Although ITGA6 and RPSA interact, they do not mutually regulate each other's expression. ITGA6 promotes invasion via the PI3K/AKT pathway (reducing p-AKT when inhibited), while RPSA acts through MAPK/ERK (reducing p-ERK1/2 when inhibited). Co-immunoprecipitation combined with mass spectrometry, siRNA knockdown, western blot for p-AKT and p-ERK1/2, invasion and metastasis assays in vitro and in vivo Experimental cell research Medium 30894280
2019 miR-143-3p directly targets ITGA6 mRNA (confirmed by dual-luciferase assay) and suppresses gallbladder cancer angiogenesis by downregulating PLGF expression via the ITGA6/PI3K/AKT pathway. Dual-luciferase reporter assay, antibody array, ELISA, western blot, PLGF rescue analysis Cell death & disease Medium 29416013
2019 NFAT1 hypermethylation in nasopharyngeal carcinoma leads to its downregulation; NFAT1 overexpression inhibits ITGA6 transcription, thereby suppressing EMT and metastasis. NFAT1 was identified as a transcriptional repressor of ITGA6 in this context. NFAT1 overexpression, invasion/migration assays, in vivo metastasis model, ChIP/reporter analysis of ITGA6 transcription Neoplasia Medium 30772768
2021 PSMC2 directly interacts with ITGA6 in hepatocellular carcinoma cells and they mutually regulate each other. Gene microarray identified ITGA6 as downstream of PSMC2; PSMC2 knockdown significantly aggravated HCC inhibition caused by ITGA6 depletion. Co-immunoprecipitation, gene microarray, ingenuity pathway analysis, siRNA knockdown, cell proliferation and invasion assays, xenograft model Cell death discovery Medium 34413286
2021 KDM5B demethylates H3K4me3 at the miR-448 promoter, suppressing miR-448 expression. miR-448 targets YTHDF3 and ITGA6 directly; thus the KDM5B/miR-448/YTHDF3/ITGA6 axis promotes HCC progression. ChIP for H3K4me3, luciferase reporter assay for miR-448 targeting YTHDF3/ITGA6, Pearson correlation, ectopic expression/depletion, xenograft model Journal of cellular and molecular medicine Medium 33829656
2021 BORG lncRNA interacts physically with the E3 SUMO ligase TRIM28, which binds to the Itga6 promoter and drives α6 integrin/CD49f expression in breast cancer stem cells. Genetic inactivation of Itga6 prevented BORG:TRIM28 complexes from inducing BCSC self-renewal, expansion, and lung metastatic outgrowth. Co-immunoprecipitation (BORG:TRIM28 interaction), ChIP (TRIM28 at Itga6 promoter), Itga6 genetic inactivation, mammosphere assay, xenotransplantation/metastasis models Molecular cancer research Medium 34497119
2021 Disruption of the SIN3A-PF1 interaction leads to increased occupancy of SIN3A and the transcriptional repressor KLF9 at the promoters of ITGA6 and ITGB1, downregulating their expression and inhibiting invasion in triple-negative breast cancer. KLF9 knockdown restored ITGA6 and ITGB1 expression and the invasive phenotype. RNA-seq, ChIP for SIN3A and KLF9 at ITGA6/ITGB1 promoters, KLF9 siRNA knockdown, invasion/migration assays, PF1-SID peptide treatment Translational oncology Medium 34968869
2021 ID1/ID3 regulate integrin α6 (Itga6) expression in skin fibroblasts, and this mechanism mediates axon guidance during wound repair. ID1/ID3-overexpressing fibroblasts showed upregulated Itga6 and directly contacted and guided regenerating axons; transplantation of these cells promoted local nerve regeneration in vivo. RNA-seq, ID1/ID3 overexpression in fibroblasts, transplantation assay, skin excision and sciatic nerve injury models, co-culture with neurons Stem cells translational medicine Medium 34520124
2024 Fucosyltransferase 8 (Fut8) directly interacts with Itga6 and catalyzes core fucosylation of Itga6 in neural stem/progenitor cells. Deletion of Fut8 enhances ubiquitination of Itga6 by promoting binding of ubiquitin ligase Trim21 to Itga6, reducing Itga6 levels and inhibiting PI3K/Akt signaling, thereby impairing adult neurogenesis. Co-immunoprecipitation (Fut8-Itga6 interaction), core fucosylation biochemical assay, Fut8 conditional knockout, ubiquitination assay, Trim21-Itga6 co-IP, PI3K/Akt pathway readout, Akt agonist rescue experiment Science China. Life sciences High 38523237
2024 ITGA6 engagement in platinum-resistant ovarian cancer activates a positive loop that stimulates IGF production/availability and over-stimulates IGF1R pathway signaling, upregulating Snail expression and promoting epithelial-mesenchymal transition and pre-metastatic niche formation. Isogenic platinum-resistant cell models, siRNA/genetic knockout, pharmacological inhibition, patient-derived models, western blot for IGF1R pathway and Snail, in vivo xenograft EMBO molecular medicine Medium 38658801
2024 ZC3H13 promotes m6A modification of ITGA6 mRNA, enhancing its stability, in bronchial epithelial cells. ZC3H13 knockdown reduced ITGA6 expression and mRNA stability (assessed by actinomycin D assay), and attenuated inflammation and fibrosis in COPD models. MeRIP-PCR for m6A modification levels, actinomycin D mRNA stability assay, siRNA knockdown, ELISA, flow cytometry, mouse COPD model with HE/Masson staining Cellular signalling Medium 38670474
2023 Targeted m6A demethylation of ITGA6 mRNA at multiple sites using a dCasRx-ALKBH5 editor significantly reduced ITGA6 protein production and inhibited bladder cancer cell proliferation and migration in vitro and tumor growth in vivo, mechanistically confirming that multi-site m6A modification drives ITGA6 mRNA translation. CRISPR-based dCasRx-m6A editing platform, MeRIP-seq, polysome profiling, single-base T3 ligase qPCR, xenograft mouse model, luciferase reporter Journal of advanced research High 37003532
2013 ITGA6 gene silencing in human thymic epithelial cells (TEC) decreases cell adhesion to laminin and downregulates expression of other laminin receptor integrin α-chains (ITGA1, ITGA2, ITGA7) while upregulating LAMA1 gene expression. ITGA6 knockdown also modulates chemokine gene expression, indicating ITGA6 participates in a broader cell migration gene network in the thymic epithelium. RNAi knockdown, flow cytometry for surface expression, cell adhesion assay to laminin, quantitative PCR for downstream gene expression, cytofluorometry BMC genomics Medium 24564203
2024 SIMALR lncRNA binds to eEF1A2 and enhances its endogenous GTPase activity; SIMALR-activated eEF1A2 phosphorylation accelerates translation of ITGB4 and ITGA6 mRNA, promoting NPC malignant phenotype. RNA-protein binding assay (SIMALR:eEF1A2), GTPase activity assay, phosphorylation assay, polysome profiling/translation assay, siRNA knockdown, in vitro and in vivo functional assays Oncogene Medium 39154122
2022 In laryngeal squamous cell carcinoma, ITGA6 accelerates Keap1 proteasomal degradation by enhancing TRIM25 expression, leading to increased Nrf2 stability and aberrant activation. ITGA6 also enhances γ-secretase-mediated Notch signaling activation, promoting RBPJ-induced TRIM25 transcription, thus connecting ITGA6 to both Nrf2 and Notch pathways. siRNA knockdown, western blot for Keap1/Nrf2/TRIM25, γ-secretase inhibitor, ChIP for RBPJ at TRIM25 promoter, co-immunoprecipitation, ubiquitination assay Cancer letters Medium 38369001
2022 ITGA6 affects trophoblast cell biological functions (proliferation, invasion, migration, apoptosis) by regulating PI3K/AKT and MAPK signaling pathways. miR-410-5p directly binds to ITGA6 3'UTR (confirmed by dual-luciferase assay) and negatively regulates ITGA6. Dual-luciferase reporter assay, siRNA knockdown, miRNA mimic/inhibitor transfection, western blot for PI3K/AKT and MAPK pathway components, functional assays Journal of reproductive immunology Medium 35667342
2012 ITGA6 knockdown alone or with ITGB1 (CD29) together produces a profound reduction in cancer stem cell migration, while knockdown of either alone has only a slight effect, revealing overlapping yet critical cooperative function of CD49f and CD29 in CSC migration. shRNA knockdown of CD29 and/or CD49f, cell migration assay, allograft mouse metastasis model Oncogene Medium 24317509

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Laminin receptor on platelets is the integrin VLA-6. Nature 685 2973567
1990 Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. Journal of immunology (Baltimore, Md. : 1950) 406 1972721
1990 Roles of adhesion molecules in T-cell recognition: fundamental similarities between four integrins on resting human T cells (LFA-1, VLA-4, VLA-5, VLA-6) in expression, binding, and costimulation. Immunological reviews 366 2196219
1990 The alpha 6 beta 1 (VLA-6) and alpha 6 beta 4 protein complexes: tissue distribution and biochemical properties. Journal of cell science 233 1698797
2019 N6-methyladenosine modification of ITGA6 mRNA promotes the development and progression of bladder cancer. EBioMedicine 174 31409574
1988 Multiple very late antigen (VLA) heterodimers on platelets. Evidence for distinct VLA-2, VLA-5 (fibronectin receptor), and VLA-6 structures. The Journal of biological chemistry 174 2967289
1995 Specific association of CD63 with the VLA-3 and VLA-6 integrins. The Journal of biological chemistry 166 7629079
2020 CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes. Neuron 161 32485136
2016 ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models. Molecular cancer 161 27001172
2010 Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance. Cancer research 148 20332234
2008 The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood 148 18818395
2017 The Role of Integrin α6 (CD49f) in Stem Cells: More than a Conserved Biomarker. Stem cells and development 141 28494695
2011 CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFβ signaling. Oncogene 139 21996747
2012 CD49f enhances multipotency and maintains stemness through the direct regulation of OCT4 and SOX2. Stem cells (Dayton, Ohio) 125 22311737
2018 miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma. Cell death & disease 94 29416013
1992 CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin VLA-6. Blood 85 1347710
2017 P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1. International journal of cancer 81 28656629
2019 ITGA6 and RPSA synergistically promote pancreatic cancer invasion and metastasis via PI3K and MAPK signaling pathways. Experimental cell research 66 30894280
2012 P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties in basal-like breast cancer. Stem cells (Dayton, Ohio) 63 22389315
2013 Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers. BMC cancer 62 23768049
2019 MicroRNA-143-3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3. Cancer science 60 30536996
2013 A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer. Oncogene 60 24317509
2017 Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT. Oncogene 59 28604746
2016 Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway. OncoTargets and therapy 57 27099513
2004 Thy1-positive mesenchymal cells promote the maturation of CD49f-positive hepatic progenitor cells in the mouse fetal liver. Hepatology (Baltimore, Md.) 57 15122765
2012 The increased expression of integrin α6 (ITGA6) enhances drug resistance in EVI1(high) leukemia. PloS one 55 22295105
2019 Urothelial organoids originating from Cd49fhigh mouse stem cells display Notch-dependent differentiation capacity. Nature communications 53 31562298
2013 CD49f-positive cell population efficiently enriches colon cancer-initiating cells. International journal of oncology 53 23708747
1995 Migration of human polymorphonuclear leukocytes through a synovial fibroblast barrier is mediated by both beta 2 (CD11/CD18) integrins and the beta 1 (CD29) integrins VLA-5 and VLA-6. Cellular immunology 47 7541723
2011 CD49f-based selection of circulating tumor cells (CTCs) improves detection across breast cancer subtypes. Cancer letters 44 22202642
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
2009 Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection. Cytometry. Part B, Clinical cytometry 42 18831072
1997 An epitope on VLA-6 (alpha6beta1) integrin involved in migration but not adhesion is required for extravasation of murine melanoma B16F1 cells in liver. Cancer research 41 9288792
2012 Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability. PloS one 40 22514625
2021 KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis. Journal of cellular and molecular medicine 35 33829656
2019 Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells. Current stem cell research & therapy 34 30280675
2015 CD49f Acts as an Inflammation Sensor to Regulate Differentiation, Adhesion, and Migration of Human Mesenchymal Stem Cells. Stem cells (Dayton, Ohio) 33 26013602
2019 MicroRNA-377-3p alleviates IL-1β-caused chondrocyte apoptosis and cartilage degradation in osteoarthritis in part by downregulating ITGA6. Biochemical and biophysical research communications 32 31831175
2023 Regulation and Functions of α6-Integrin (CD49f) in Cancer Biology. Cancers 31 37444576
2018 MiR-127-3p inhibits cell growth and invasiveness by targeting ITGA6 in human osteosarcoma. IUBMB life 31 29573114
2018 Gliomasphere marker combinatorics: multidimensional flow cytometry detects CD44+/CD133+/ITGA6+/CD36+ signature. Journal of cellular and molecular medicine 31 30467961
2013 CD49f(high) cells retain sphere-forming and tumor-initiating activities in human gastric tumors. PloS one 31 24015244
2012 CD49f is an efficient marker of monolayer- and spheroid colony-forming cells of the benign and malignant human prostate. PloS one 31 23071686
2012 Human osteosarcoma CD49f(-)CD133(+) cells: impaired in osteogenic fate while gain of tumorigenicity. Oncogene 30 23045288
2020 Exosomal miR-126 blocks the development of non-small cell lung cancer through the inhibition of ITGA6. Cancer cell international 29 33317527
2015 CD34 and CD49f Double-Positive and Lineage Marker-Negative Cells Isolated from Human Myometrium Exhibit Stem Cell-Like Properties Involved in Pregnancy-Induced Uterine Remodeling. Biology of reproduction 29 26108791
2012 In vitro production of haploid cells after coculture of CD49f+ with Sertoli cells from testicular sperm extraction in nonobstructive azoospermic patients. Fertility and sterility 29 22732736
2024 m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways. Cancer letters 28 38369001
2019 Long non-coding RNA activated by transforming growth factor-β promotes proliferation and invasion of cervical cancer cells by regulating the miR-144/ITGA6 axis. Experimental physiology 26 30908730
2018 Ex Vivo Expansion of CD34+ CD90+ CD49f+ Hematopoietic Stem and Progenitor Cells from Non-Enriched Umbilical Cord Blood with Azole Compounds. Stem cells translational medicine 26 29392885
2018 MYC Regulates α6 Integrin Subunit Expression and Splicing Under Its Pro-Proliferative ITGA6A Form in Colorectal Cancer Cells. Cancers 25 29401653
2014 CD49f-positive testicular cells in Saanen dairy goat were identified as spermatogonia-like cells by miRNA profiling analysis. Journal of cellular biochemistry 25 24817091
2013 ITGA6 gene silencing by RNA interference modulates the expression of a large number of cell migration-related genes in human thymic epithelial cells. BMC genomics 25 24564203
2021 Molecular Pathogenesis and Regulation of the miR-29-3p-Family: Involvement of ITGA6 and ITGB1 in Intra-Hepatic Cholangiocarcinoma. Cancers 24 34199886
2017 CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer. Journal of breast cancer 24 28690650
2021 ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair. Stem cells translational medicine 23 34520124
2016 RETRACTED: Twist2 promotes kidney cancer cell proliferation and invasion via regulating ITGA6 and CD44 expression in the ECM-Receptor-Interaction pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 27261625
2017 SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment. Stem cell reports 22 28132885
2024 Ac4C modification of lncRNA SIMALR promotes nasopharyngeal carcinoma progression through activating eEF1A2 to facilitate ITGB4/ITGA6 translation. Oncogene 21 39154122
2023 Targeted m6A demethylation of ITGA6 mRNA by a multisite dCasRx-m6A editor inhibits bladder cancer development. Journal of advanced research 21 37003532
2013 Expression of stem cell markers: OCT4, KIT, ITGA6, and ITGB1 in the male germinal epithelium. Systems biology in reproductive medicine 21 23758503
1995 CD49f (alpha 6 integrin) and CD66a (BGP) are specifically induced by retinoids during human monocytic differentiation. Leukemia 21 8609714
2021 LncRNA SNHG16 promotes epithelial-mesenchymal transition by upregulating ITGA6 through miR-488 inhibition in osteosarcoma. Journal of bone oncology 20 33598394
2021 PSMC2/ITGA6 axis plays critical role in the development and progression of hepatocellular carcinoma. Cell death discovery 20 34413286
2022 The miR-410-5p /ITGA6 axis participates in the pathogenesis of recurrent abortion by regulating the biological function of trophoblast. Journal of reproductive immunology 19 35667342
2016 Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential. Aging 19 27852980
2016 CD66 and CD49f expressing cells are associated with distinct neoplastic phenotypes and progression in human cervical cancer. European journal of cancer (Oxford, England : 1990) 18 27132080
1995 Regulation of polymorphonuclear neutrophil CD16 and CD11b/CD18 expression by matrix proteins during hypoxia is VLA-5, VLA-6 dependent. Journal of immunology (Baltimore, Md. : 1950) 18 7594504
2024 ZC3H13 promotes ITGA6 m6A modification for chronic obstructive pulmonary disease progression. Cellular signalling 17 38670474
2022 The circ-PITX1 promotes non-small cell lung cancer development via the miR-30e-5p/ITGA6 axis. Cell cycle (Georgetown, Tex.) 17 35007184
2024 Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway. Science China. Life sciences 16 38523237
2021 lncRNA BORG:TRIM28 Complexes Drive Metastatic Progression by Inducing α6 Integrin/CD49f Expression in Breast Cancer Stem Cells. Molecular cancer research : MCR 16 34497119
2020 Isolation of Human CD49f+ Astrocytes and In Vitro iPSC-Based Neurotoxicity Assays. STAR protocols 16 33377066
2019 Peptide-Targeted Polyplexes for Aerosol-Mediated Gene Delivery to CD49f-Overexpressing Tumor Lesions in Lung. Molecular therapy. Nucleic acids 16 31734558
2022 Long non-coding RNA OIP5-AS1 suppresses microRNA-92a to augment proliferation and metastasis of ovarian cancer cells through upregulating ITGA6. Journal of ovarian research 15 35168644
2022 Effect of different iodine levels on the DNA methylation of PRKAA2, ITGA6, THEM4 and PRL genes in PI3K-AKT signaling pathway and population-based validation from autoimmune thyroiditis patients. European journal of nutrition 15 35622138
2021 Downregulation of ITGA6 confers to the invasion of multiple myeloma and promotes progression to plasma cell leukaemia. British journal of cancer 15 33785876
2021 Invasive phenotype in triple negative breast cancer is inhibited by blocking SIN3A-PF1 interaction through KLF9 mediated repression of ITGA6 and ITGB1. Translational oncology 15 34968869
2019 NFAT1 Hypermethylation Promotes Epithelial-Mesenchymal Transition and Metastasis in Nasopharyngeal Carcinoma by Activating ITGA6 Transcription. Neoplasia (New York, N.Y.) 15 30772768
2019 CD49fhigh Defines a Distinct Skin Mesenchymal Stem Cell Population Capable of Hair Follicle Epithelial Cell Maintenance. The Journal of investigative dermatology 15 31494092
2016 Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells. Oncotarget 15 27374087
2021 PRR34-AS1 sponges miR-498 to facilitate TOMM20 and ITGA6 mediated tumor progression in HCC. Experimental and molecular pathology 14 33609562
2021 Evaluation of CD49f as a novel surface marker to identify functional adipose-derived mesenchymal stem cell subset. Cell proliferation 14 33704842
2019 MiR-302a-5p suppresses cell proliferation and invasion in non-small cell lung carcinoma by targeting ITGA6. American journal of translational research 14 31396340
2010 Effects of Wnt-10b on proliferation and differentiation of adult murine skin-derived CD34 and CD49f double-positive cells. Journal of bioscience and bioengineering 14 20547359
2024 Platinum-induced upregulation of ITGA6 promotes chemoresistance and spreading in ovarian cancer. EMBO molecular medicine 13 38658801
2021 LncRNA DRAIC regulates cell proliferation and migration by affecting the miR-34a-5p/ITGA6 signal axis in Hirschsprung's disease. Upsala journal of medical sciences 13 34471485
2020 PAX7 promotes CD49f-positive dairy goat spermatogonial stem cells' self-renewal. Journal of cellular physiology 13 32692417
2017 Distinct mechanisms of regulation of the ITGA6 and ITGB4 genes by RUNX1 in myeloid cells. Journal of cellular physiology 13 28926098
2014 High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures. Cancer medicine 13 24802970
1996 Integrin VLA-6 (alpha 6 beta 1) mediates adhesion of mouse bone marrow-derived mast cells to laminin. Allergy 13 8899118
2016 RFX1 maintains testis cord integrity by regulating the expression of Itga6 in male mouse embryos. Molecular reproduction and development 12 27228460
2000 Alpha 6 beta 1 integrin (VLA-6) mediates leukocyte tether and arrest on laminin under physiological shear flow. Cellular immunology 12 10698619
1995 VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity following autologous or allogeneic bone marrow transplantation. Experimental hematology 12 8542943
1992 Differential increase in 12-HETE release and CD29/CD49f expression of platelets from normal donors and from patients with atopic dermatitis by Staphylococcus aureus. International archives of allergy and immunology 12 1384866
2022 miR-186-5p inhibits the progression of oral squamous cell carcinoma by targeting ITGA6 to impair the activity of the PI3K/AKT pathway. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 11 35201653
2022 Extracellular vesicle-mediated delivery of miR-127-3p inhibits the proliferation and invasion of choriocarcinoma cells by targeting ITGA6. Experimental cell research 11 35288170
2022 Integrin α6A (ITGA6A)-type Splice Variant in Extracellular Vesicles Has a Potential as a Novel Marker of the Early Recurrence of Pancreatic Cancer. Anticancer research 11 35346995
2020 Comparing genome-scale DNA methylation and CNV marks between adult human cultured ITGA6+ testicular cells and seminomas to assess in vitro genomic stability. PloS one 10 32176716
2020 Pranlukast Antagonizes CD49f and Reduces Stemness in Triple-Negative Breast Cancer Cells. Drug design, development and therapy 10 32494122

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