Affinage

ITGB8

Integrin beta-8 · UniProt P26012

Length
769 aa
Mass
85.6 kDa
Annotated
2026-06-10
27 papers in source corpus 10 papers cited in narrative 10 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

ITGB8 is a transmembrane integrin subunit that operates as a cell-surface receptor coupling extracellular ligand engagement to intracellular signaling that governs tissue remodeling, differentiation, and reproductive processes (PMID:41813908, PMID:25788663). A core function is the activation of latent TGF-β1: during preimplantation, ITGB8 promotes release of active TGF-β1 and downstream SMAD2/3 phosphorylation, and parallel FAK-dependent signaling through ITGB8→FAK→VAV→RAC1 is required for blastocyst attachment in endometrial epithelium (PMID:25788663, PMID:28507287). ITGB8 transduces FAK-anchored cascades in other contexts as well, supporting FAK→ERK→RUNX2 signaling that balances osteogenic versus adipogenic differentiation of mesenchymal stem cells (PMID:41878635). In bone homeostasis, osteoblast-derived osteomodulin engages ITGB8 on osteoclast precursors to suppress RhoA, enhance YAP phosphorylation, and repress YAP/TEAD-driven RRM2 transcription, lowering mitochondrial respiration and restraining osteoclastogenesis (PMID:41813908). ITGB8 expression is transcriptionally driven by EBF1 in fibrotic bone-marrow stromal cells (PMID:41756923) and is post-transcriptionally constrained by 3'-UTR-targeting miRNAs including miR-199a-3p and miR-187 (PMID:29436681, PMID:41878635, PMID:34973644). Its expression is associated with chemoresistance and tumor signaling in cancer settings (PMID:29436681).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2015 Medium

    Establishing that ITGB8 controls latent TGF-β1 activation in vivo defined its first concrete molecular role in tissue signaling during embryo implantation.

    Evidence Antibody bioneutralization and siRNA silencing of Itgb8 in mouse uterus, with active TGF-β1 and phospho-SMAD2/3 readouts

    PMID:25788663

    Open questions at the time
    • Mechanism of how ITGB8 binds and presents latent TGF-β1 not structurally resolved
    • Single lab, no independent replication
  2. 2015 Low

    Linking ITGB8 to TGF-β-dependent multidrug resistance extended its signaling role into cancer phenotypes.

    Evidence siRNA knockdown in HepG2/G hepatic cancer cells with drug-resistance protein and TGF-β component Western blots

    PMID:25932283

    Open questions at the time
    • Pathway placement inferred from expression changes only
    • No direct demonstration of ITGB8-driven TGF-β activation in this context
  3. 2017 Medium

    Defining the ITGB8→FAK→VAV→RAC1 axis showed ITGB8 transduces an intracellular cytoskeletal/GTPase signaling cascade required for blastocyst attachment.

    Evidence Reciprocal ITGB8 siRNA knockdown and FAK inhibition with phospho-FAK, phospho-VAV, RAC1-GTP, and spheroid attachment assays

    PMID:28507287

    Open questions at the time
    • Ligand initiating the cascade not defined
    • No structural detail of receptor-effector coupling
  4. 2018 Medium

    Identifying ITGB8 as a direct miR-199a-3p target established post-transcriptional control of ITGB8 governing chemosensitivity.

    Evidence 3'-UTR luciferase reporter, rescue overexpression, and orthotopic mouse model in ovarian cancer cells

    PMID:29436681

    Open questions at the time
    • Downstream effector pathway of ITGB8 in cisplatin resistance not resolved
    • Single lab
  5. 2020 Low

    Placing ITGB8 downstream of a PVT1/miR-145-5p axis tied it to MEK/ERK activation in lung cancer.

    Evidence PVT1 knockdown, miR-145-5p luciferase binding, p-MEK/p-ERK Western blot, and ITGB8 rescue in NSCLC xenografts

    PMID:32202906

    Open questions at the time
    • No direct demonstration of ITGB8-mediated MEK/ERK activation
    • Pathway relies on rescue and expression correlation
  6. 2021 Low

    Validating miR-187 as a direct ITGB8 regulator linked to IFNT signaling extended miRNA control of ITGB8 to conceptus attachment.

    Evidence Dual-luciferase 3'-UTR assay, miR-187 inhibition, and FAK activity readout in goat endometrial epithelial cells

    PMID:34973644

    Open questions at the time
    • Functional follow-up limited to single cell-based assays
    • No in vivo validation
  7. 2023 Low

    Embedding ITGB8 in a mechanosensitive F-actin/ITGB8/TRIM59/AKT/mTOR axis connected it to biomechanically driven tumor stemness.

    Evidence Atomic force microscopy, microfluidic soft-cell isolation, and Western blot for ITGB8/TRIM59/p-AKT in bladder cancer

    PMID:37390491

    Open questions at the time
    • Pathway ordering correlative without direct ITGB8 manipulation
    • Single lab
  8. 2026 High

    Resolving the OMD→ITGB8→RhoA→YAP→RRM2→mitochondrial respiration pathway gave ITGB8 a defined ligand and a multi-step mechanism controlling osteoclastogenesis.

    Evidence Global and cell-type-specific Omd/Itgb8 mouse models, recombinant OMD reconstitution, ChIP for YAP/TEAD at RRM2, and bioenergetics assays

    PMID:41813908

    Open questions at the time
    • Structural basis of OMD-ITGB8 engagement not defined
    • Generalizability beyond bone not tested
  9. 2026 Medium

    Showing EBF1 directly drives ITGB8 in fibrotic stromal cells identified a transcriptional regulator and a disease role in myelofibrosis.

    Evidence MSC-specific Itgb8 knockout and neutralizing antibody in MPL W515L myelofibrosis mice, with EBF1 ChIP/regulation studies

    PMID:41756923

    Open questions at the time
    • Preprint, not peer-reviewed
    • ITGB8 effector mechanism driving fibrosis not detailed
  10. 2026 Medium

    Demonstrating miR-199a-3p suppression of ITGB8→FAK→ERK→RUNX2 defined an ITGB8 differentiation-control axis relevant to osteonecrosis.

    Evidence Dual-luciferase assay, mRNA-seq, miR-199a-3p modulation, and antagomiR in a SONFH rat model with phospho-FAK/ERK/RUNX2 readouts

    PMID:41878635

    Open questions at the time
    • Upstream ligand for FAK activation not identified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis and ligand-binding determinants by which ITGB8 selects among latent TGF-β1, osteomodulin, and other matrix ligands to direct distinct downstream cascades remain unresolved.
  • No structural model of ITGB8 ligand engagement in corpus
  • Determinants of context-specific FAK vs RhoA/YAP output unknown
  • Heterodimer partner subunit not characterized in timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 1
Partners

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 ITGB8 activates VAV-RAC1 signaling via FAK in endometrial epithelial cells: ITGB8 knockdown reduced phosphorylated-FAK, phosphorylated-VAV, and GTP-bound RAC1, and FAK inhibition also blocked VAV/RAC1 activation, establishing a functional ITGB8→FAK→VAV→RAC1 signaling axis required for blastocyst attachment. siRNA knockdown of ITGB8 in endometrial epithelial cells and uterus, FAK inhibition, measurement of phospho-FAK (Y397), phospho-VAV, RAC1-GTP pull-down, JAr spheroid attachment assay Scientific reports Medium 28507287
2015 ITGB8 regulates activation of latent TGF-β1 in the uterus: bioneutralization or mRNA silencing of Itgb8 at the preimplantation stage reduced active TGF-β1 release and downstream SMAD2/3 phosphorylation, linking ITGB8 to TGF-β1 activation during embryo implantation. Antibody-mediated bioneutralization of ITGB8, siRNA silencing in mouse uterus, measurement of active TGF-β1 and phospho-SMAD2/3, embryo implantation rate assessment Biology of reproduction Medium 25788663
2015 ITGB8 overexpression is associated with gefitinib resistance in hepatic cancer cells, and ITGB8 silencing reverses resistance by reducing ABCB1, ABCC2, ABCG2, survivin, Bcl-2, and CDK1; the TGF-β pathway was implicated as a critical mediator of ITGB8-dependent drug resistance. siRNA knockdown of ITGB8 in HepG2/G cells, cell proliferation and apoptosis assays, Western blot for multidrug-resistance proteins and TGF-β pathway components International journal of clinical and experimental medicine Low 25932283
2018 miR-199a-3p directly targets the 3'-UTR of ITGB8 and suppresses its expression; overexpression of ITGB8 rescued cisplatin resistance that was inhibited by miR-199a-3p, placing ITGB8 downstream of miR-199a-3p in control of cisplatin sensitivity in ovarian cancer cells. Luciferase reporter assay (3'-UTR binding), Western blot, miR-199a-3p overexpression/inhibition, ITGB8 rescue overexpression, cell proliferation, invasion, apoptosis, and in vivo orthotopic mouse model Oncology reports Medium 29436681
2020 ITGB8 acts downstream of the lncRNA PVT1/miR-145-5p axis to activate the MEK/ERK signaling pathway in NSCLC; PVT1 knockdown suppressed ITGB8 expression and reduced MEK/ERK phosphorylation, while ITGB8 overexpression rescued these effects. siRNA/shRNA knockdown of PVT1, luciferase reporter assay for miR-145-5p binding, Western blot for p-MEK and p-ERK, ITGB8 rescue overexpression, xenograft tumor model Neoplasma Low 32202906
2021 In goat endometrial epithelial cells, ITGB8 is a direct target of miR-187 (validated by 3'-UTR luciferase assay); inhibition of miR-187 upregulated ITGB8 and reduced FAK activity and cell proliferation, and both ITGB8 and miR-187 are regulated by interferon tau (IFNT), placing ITGB8 downstream of IFNT signaling during conceptus attachment. qRT-PCR, Western blot, dual-luciferase reporter assay in primary goat endometrial epithelial cells (EECs), miR-187 inhibition, FAK activity measurement Theriogenology Low 34973644
2023 In bladder cancer, biomechanical stimuli from 3D Matrigel activate an F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathway; Western blotting confirmed upregulation of ITGB8, TRIM59, and phospho-AKT in soft tumor cells, and this axis was associated with tumor softness, stemness, and recurrence. Atomic force microscopy, microfluidic isolation of soft cells, Western blot for ITGB8/TRIM59/p-AKT/mTOR, double immunostaining for F-actin/TRIM59, colony formation assay, xenograft tumor model Chinese medical journal Low 37390491
2026 Osteoblast-derived osteomodulin (OMD) engages integrin β8 on osteoclast precursors to suppress RhoA activity and enhance YAP phosphorylation, thereby reducing YAP/TEAD occupancy at the RRM2 promoter, repressing RRM2 transcription, decreasing mtDNA copy number and electron transport chain protein abundance, and reducing mitochondrial respiration and ATP production to restrain osteoclastogenesis. Osteoblast/MSC-specific and global Omd deletion mouse models, osteoclast precursor-specific deletion, recombinant OMD supplementation, pharmacologic RRM2 inhibition, ChIP (YAP/TEAD at RRM2 promoter), mitochondrial respiration assays, ITGB8-OMD interaction studies, ovariectomy and LPS bone-loss models Experimental & molecular medicine High 41813908
2026 Transcription factor EBF1 directly regulates ITGB8 expression in bone marrow mesenchymal stromal cells (MSCs); MSC-specific deletion of Itgb8 or ITGB8-neutralizing antibody treatment in myelofibrosis mice reduced BM fibrosis, decreased MPL-mutant cell frequencies, and reduced BM inflammation, establishing ITGB8 as a downstream effector of EBF1 in the fibrotic MSC gene program. MSC-specific conditional Itgb8 knockout mice (MPL W515L transplant MF model), ITGB8-neutralizing antibody treatment, EBF1 ChIP/gene regulation studies, histology and flow cytometry for fibrosis and myeloid expansion bioRxivpreprint Medium 41756923
2026 miR-199a-3p directly targets ITGB8 (confirmed by dual-luciferase reporter assay) and suppresses FAK-ERK-RUNX2 signaling in bone marrow mesenchymal stem cells; silencing miR-199a-3p restored ITGB8 levels and reactivated FAK-ERK-RUNX2, correcting the osteogenic/adipogenic differentiation imbalance in steroid-induced osteonecrosis of the femoral head. Dual-luciferase reporter assay, mRNA-seq, miR-199a-3p overexpression/inhibition in BMSCs, Western blot for phospho-FAK, phospho-ERK, RUNX2, antagomiR-199a-3p in vivo in SONFH rat model Research (Washington, D.C.) Medium 41878635

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling. Molecular therapy : the journal of the American Society of Gene Therapy 132 34371180
2020 Circular RNA TTBK2 regulates cell proliferation, invasion and ferroptosis via miR-761/ITGB8 axis in glioma. European review for medical and pharmacological sciences 87 32196629
2018 A novel circular RNA, hsa_circ_0046701, promotes carcinogenesis by increasing the expression of miR-142-3p target ITGB8 in glioma. Biochemical and biophysical research communications 73 29337055
2018 miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8. Oncology reports 67 29436681
2017 miR19b-3p promotes the growth and metastasis of colorectal cancer via directly targeting ITGB8. American journal of cancer research 36 29119049
2017 Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation. Scientific reports 35 28507287
2020 The long non-coding RNA PVT1/miR-145-5p/ITGB8 axis regulates cell proliferation, apoptosis, migration and invasion in non-small cell lung cancer cells. Neoplasma 28 32202906
2018 miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its Target Genes TGFBR2, ITGB8, and LATS2. Molecular therapy oncolytics 28 30294667
2022 Exosomal circDNER enhances paclitaxel resistance and tumorigenicity of lung cancer via targeting miR-139-5p/ITGB8. Thoracic cancer 26 35396925
2015 Integrin beta 8 (ITGB8) regulates embryo implantation potentially via controlling the activity of TGF-B1 in mice. Biology of reproduction 26 25788663
2015 Integrin beta-8 (ITGB8) silencing reverses gefitinib resistance of human hepatic cancer HepG2/G cell line. International journal of clinical and experimental medicine 25 25932283
2019 miR‑222 regulates brain injury and inflammation following intracerebral hemorrhage by targeting ITGB8. Molecular medicine reports 24 31894320
2018 Integrin Subunit beta 8 (ITGB8) Upregulation Is an Independent Predictor of Unfavorable Survival of High-Grade Serous Ovarian Carcinoma Patients. Medical science monitor : international medical journal of experimental and clinical research 23 30531684
2020 LncRNA FEZF1-AS1 promoted chemoresistance, autophagy and epithelial-mesenchymal transition (EMT) through regulation of miR-25-3p/ITGB8 axis in prostate cancer. European review for medical and pharmacological sciences 13 32196579
2021 Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis. Open life sciences 11 34250246
2021 LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness via Regulating ITGB8. Frontiers in oncology 11 34868900
2021 Circ_0017956 promotes the proliferation and metastasis of non-small cell lung cancer through regulating miR-515-5p/ITGB8 axis. Cell cycle (Georgetown, Tex.) 10 33945401
2021 Peri-implantation expression and regulation of ITGB8 in goat uterus. Theriogenology 9 34973644
2024 Investigating the inflammatory mechanism of notoginsenoside R1 in Diabetic nephropathy via ITGB8 based on network pharmacology and experimental validation. Molecular medicine (Cambridge, Mass.) 7 39725889
2023 Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer. Chinese medical journal 7 37390491
2023 miR-199-3p suppresses cellular migration and viability and promotes progesterone production in goose ovarian follicles before selection through regulating ITGB8 and other ECM-related genes. British poultry science 5 36598846
2021 Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis. Open life sciences 5 34017919
2024 A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background. Journal of ovarian research 2 39506768
2025 Evaluation of Salivary, Plasma, and Tissue ITGB8 and MIAT-lncRNA Expression as a Biomarker in Oral Squamous Cell Carcinoma: A Cross-Sectional Study. Biochemical genetics 1 41015604
2026 Inhibition of the EBF1-ITGB8 Axis in Bone Marrow Niche Ameliorates Hallmarks of Myelofibrosis. bioRxiv : the preprint server for biology 0 41756923
2026 Osteoblast-derived osteomodulin restrains osteoclastogenesis via ITGB8/RRM2-mediated reduction of mitochondrial respiration and mitochondrial ATP production. Experimental & molecular medicine 0 41813908
2026 miR-199a-3p Promotes Adipogenic Differentiation to Aggravate Steroid-Induced Osteonecrosis of Femoral Head via the ITGB8/FAK-ERK/RUNX2 Pathway. Research (Washington, D.C.) 0 41878635

Missed literature

Know a paper Affinage missed for ITGB8? Flag it for the maintainers and the community.

No submissions yet.