Affinage

ITGBL1

Integrin beta-like protein 1 · UniProt O95965

Length
494 aa
Mass
53.9 kDa
Annotated
2026-06-10
92 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGBL1 (TIED) is a secreted extracellular protein built from a signal peptide and ten tandem integrin-beta-like EGF repeats that functions as an extracellular regulator of integrin activity in cell migration, tissue homeostasis, and cancer progression (PMID:10051402, PMID:30305454). Unlike cytosolic integrin inhibitors, ITGBL1 physically engages integrins from outside the cell to down-regulate integrin-ECM binding, a mechanism that protects articular cartilage and promotes chondrogenesis (PMID:30305454), and that it deploys spatially by preferentially disassembling focal adhesions at the trailing edge of migrating cells to drive directional motility (PMID:35066808). Its expression is governed by a multilayered regulatory network: transcriptional activation by RUNX2 (which itself is de-repressed upon loss of MITF) and suppression by JDP2 at the promoter (PMID:26060017, PMID:33413419, PMID:35584452, PMID:40287769); epigenetic control via SMYD3-dependent H3K4me3 downstream of the integrin-beta1/ILK/TCF-4 mechanotransduction axis (PMID:37192621); m6A-dependent mRNA stabilization by RBM15 (PMID:39840822); and post-translational turnover through HSP90AB1-mediated K63-linked ubiquitination (PMID:41697125). Functionally, ITGBL1 couples to multiple downstream signaling outputs depending on context — TGF-beta/Smad signaling in bone metastasis, hepatocellular and pancreatic cancer and fibrosis (PMID:26060017, PMID:32537856, PMID:35584452, PMID:30528088), NF-kappaB signaling in prostate cancer and in fibroblast activation (PMID:32139701, PMID:31190876), AKT/Fibulin-2 signaling in gastric cancer anoikis resistance and metastasis (PMID:33049688, PMID:38332530), and Wnt/PCP signaling (PMID:26307393, PMID:27261588). When packaged into extracellular vesicles, ITGBL1 activates resident fibroblasts via a TNFAIP3-NF-kappaB axis to elicit IL-6/IL-8 secretion and establish pre-metastatic niches (PMID:32139701, PMID:35381565), while fibroblast-derived ITGBL1 vesicles drive collagen synthesis and skin fibrosis through TGF-beta1/SMAD2/3 (PMID:35733144). ITGBL1 thus behaves context-dependently, acting as a metastasis- and fibrosis-promoting factor in most epithelial cancers and connective tissue settings yet as a Wnt/PCP-restraining tumor suppressor in NSCLC (PMID:26307393).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 Medium

    Established the molecular identity of ITGBL1 as a secreted protein whose ten tandem EGF-like repeats mimic the cysteine-rich stalk of integrin beta subunits, framing the hypothesis that it acts in the integrin-ECM axis.

    Evidence cDNA cloning from fetal lung/HUVEC/osteoblast libraries with Northern blot and chromosomal mapping

    PMID:10051402

    Open questions at the time
    • No functional or binding partner demonstrated at cloning
    • Tissue expression limited to aorta, thymus, osteosarcoma cells
  2. 2015 Medium

    Placed ITGBL1 in a defined oncogenic circuit as a RUNX2-induced effector activating TGF-beta signaling to drive breast cancer bone metastasis, while a parallel report cast it as a Wnt/PCP-restraining tumor suppressor in NSCLC — establishing context-dependent function.

    Evidence In vivo bone metastasis model with loss/gain-of-function and TGF-beta pathway analysis; siRNA/recombinant protein assays with Wnt/PCP analysis in NSCLC

    PMID:26060017 PMID:26307393

    Open questions at the time
    • Opposite directionality across tissues not mechanistically reconciled
    • RUNX2-ITGBL1 promoter binding not yet demonstrated directly
  3. 2016 Medium

    Showed recombinant ITGBL1 promotes ovarian cancer migration/adhesion dose-dependently and modulates Wnt/PCP and FAK/Src signaling, linking the secreted protein to adhesion machinery.

    Evidence Recombinant protein treatment, transwell/wound healing, pathway analysis

    PMID:27261588

    Open questions at the time
    • Direct integrin engagement not shown here
    • Single lab, no in vivo validation
  4. 2018 High

    Demonstrated the core molecular mechanism — ITGBL1 physically binds integrins extracellularly to down-regulate integrin activity, protecting cartilage and promoting chondrogenesis, distinguishing it from cytosolic integrin inhibitors.

    Evidence Co-IP physical interaction assays, chondrocyte loss/gain-of-function, Xenopus and DMM mouse OA models, recombinant protein rescue

    PMID:30305454

    Open questions at the time
    • Which integrin heterodimers are bound not fully resolved
    • Structural basis of the interaction not determined
  5. 2018 Medium

    Identified an upstream epigenetic regulatory layer in which the lncRNA lncITPF (dependent on its host gene ITGBL1) recruits hnRNP-L to control histone acetylation at the ITGBL1 promoter, downstream of TGF-beta1-Smad2/3 in pulmonary fibrosis.

    Evidence RNA pull-down, LC-MS, ChIP-qPCR, CRISPR-Cas9, RACE, promoter activity assays

    PMID:30528088

    Open questions at the time
    • Finding concerns ITGBL1 expression regulation, not protein mechanism
    • Direct ITGBL1 protein output in fibrosis not assayed here
  6. 2019 Medium

    Extended ITGBL1's oncogenic output to NF-kappaB signaling driving EMT, migration, and invasion in prostate cancer.

    Evidence RT-qPCR, Western blot, migration/invasion assays, NF-kappaB analysis, xenografts

    PMID:31190876

    Open questions at the time
    • How secreted ITGBL1 engages NF-kappaB upstream not defined
    • Single lab
  7. 2020 High

    Revealed a non-cell-autonomous metastatic mechanism: tumor-released ITGBL1-rich EVs activate remote fibroblasts via TNFAIP3-NF-kappaB to secrete IL-6/IL-8 and build pre-metastatic niches.

    Evidence EV isolation, fibroblast activation assays, ELISA, NF-kappaB Western blot, in vivo metastasis models

    PMID:32139701

    Open questions at the time
    • Receptor on recipient fibroblasts not identified
    • How ITGBL1 is sorted into EVs unknown
  8. 2020 Medium

    Linked ITGBL1 to TGF-beta/Smads signaling and KRT17/EMT induction in hepatocellular carcinoma migration and invasion.

    Evidence Western blot, RT-PCR, transwell assays, xenograft and orthotopic mouse models

    PMID:32537856

    Open questions at the time
    • Mechanism connecting secreted ITGBL1 to intracellular Smads not resolved
  9. 2021 Medium

    Defined ITGBL1 as an immune-evasion factor: loss of MITF de-represses RUNX2, upregulating ITGBL1 to inhibit NK cytotoxicity and counter anti-PD1 therapy in melanoma.

    Evidence NK cytotoxicity assays, in vivo anti-PD1 models, MITF/RUNX2/ITGBL1 manipulation, Vitamin D3 (RUNX2 inhibitor)

    PMID:33413419

    Open questions at the time
    • Molecular target of ITGBL1 on NK cells unknown
    • Direct RUNX2 promoter binding not shown in this study
  10. 2021 Medium

    Added AKT signaling as an output of ITGBL1 driving gastric cancer proliferation and motility.

    Evidence Western blot for Akt phosphorylation, gain/loss-of-function, proliferation/migration assays

    PMID:33049688

    Open questions at the time
    • Upstream coupling of secreted ITGBL1 to AKT not defined
  11. 2022 Medium

    Resolved the spatial logic of ITGBL1 in migration — it preferentially inhibits integrin and disassembles focal adhesions at the trailing edge to enable directional motility.

    Evidence siRNA/overexpression, wound healing, live imaging of membrane-GFP cells, active integrin/FAK/Vinculin immunostaining

    PMID:35066808

    Open questions at the time
    • What spatially restricts ITGBL1 action to the trailing edge is unknown
    • Single lab
  12. 2022 Medium

    Mapped additional regulatory and effector arms: JDP2 directly represses the ITGBL1 promoter in pancreatic cancer; fibroblast-derived ITGBL1 EVs drive skin fibrosis via TGF-beta1/SMAD2/3; and a TCM recipe blunts CRC metastasis by lowering EV ITGBL1 and the TNFAIP3-NF-kappaB axis.

    Evidence Dual-luciferase promoter assays, LC-MS/MS EV proteomics, in vivo skin and liver metastasis models, Western blot/ELISA

    PMID:35381565 PMID:35584452 PMID:35733144

    Open questions at the time
    • Whether TGF-beta/Smad activation is direct or secondary to integrin modulation unresolved
  13. 2024 Medium

    Identified the AKT/Fibulin-2 axis as the mechanism by which ITGBL1 confers anoikis resistance and metastatic capacity in gastric cancer.

    Evidence Gain/loss-of-function, anoikis assays, in vivo metastasis models, AKT/FBLN2 pathway inhibition rescue

    PMID:38332530

    Open questions at the time
    • How ITGBL1 engages AKT/FBLN2 at the molecular level unclear
  14. 2025 High

    Established direct transcriptional and post-transcriptional control: RUNX2 directly binds the ITGBL1 promoter to drive hepatic stellate cell activation/liver fibrosis, and RBM15 stabilizes ITGBL1 mRNA via m6A to promote colon cancer immune suppression.

    Evidence ChIP and luciferase reporter assays (RUNX2), MeRIP and dual-luciferase (RBM15), in vivo HBV and xenograft models, pharmacological RUNX2 inhibition

    PMID:39840822 PMID:40287769

    Open questions at the time
    • Reader proteins downstream of m6A marks not identified
    • Integration of the two regulatory layers not tested
  15. 2026 Medium

    Defined post-translational turnover and a cell-intrinsic stress role: HSP90AB1 binds ITGBL1 and targets it for K63-linked ubiquitin-proteasome degradation, while ITGBL1 itself triggers ROS-driven ER stress and autophagy in osteosarcoma.

    Evidence Co-IP, virtual drug screening (Ivermectin), ubiquitination/ER-stress Western blot, ROS and autophagy assays, in vivo osteosarcoma model

    PMID:41697125

    Open questions at the time
    • Single Co-IP for HSP90AB1 interaction without reciprocal structural validation
    • Link between ER stress/autophagy and integrin function unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the specific integrin heterodimer(s) and any co-receptor through which secreted or EV-borne ITGBL1 transduces the diverse TGF-beta/Smad, NF-kappaB, AKT, and Wnt/PCP outputs remains unresolved, as does the structural basis for its integrin antagonism.
  • No structural model of the ITGBL1-integrin complex
  • Receptor on recipient fibroblasts/immune cells unknown
  • Mechanism reconciling tumor-suppressor vs metastasis-promoting roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2 GO:0031012 extracellular matrix 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
HSP90AB1ITGB1

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 ITGBL1 (TIED) was cloned and characterized as a novel secreted protein comprising a signal peptide followed by 10 tandem EGF-like repeats strikingly similar to the cysteine-rich stalk-like structure of integrin beta subunits, with the EGF-like repeats containing 8 cysteines in positions distinct from laminin/fibrillin EGF domains. ITGBL1 mRNA (2.8 kb) was detected in aorta, thymus, and osteogenic sarcoma cells, and the gene was mapped to chromosome 13q33. cDNA cloning from fetal lung, HUVEC, and osteoblast libraries; Northern blot; chromosomal mapping Genomics Medium 10051402
2015 ITGBL1 promotes breast cancer bone metastasis by activating the TGF-β signaling pathway as a downstream effector, and is transcriptionally activated upstream by the transcription factor Runx2. ITGBL1 expression facilitated recruitment, residence, and growth of cancer cells in bone microenvironment and osteoclast maturation to form osteolytic lesions in vivo and in vitro. ITGBL1 was identified as an essential mediator of Runx2-induced bone metastasis. In vivo mouse bone metastasis model, in vitro functional assays, Western blotting for TGF-β pathway, loss/gain-of-function experiments Cancer research Medium 26060017
2018 ITGBL1 is a secreted protein that physically interacts with integrins extracellularly to down-regulate integrin activity, thereby promoting chondrogenesis. Unlike cytosolic integrin inhibitors, ITGBL1 acts from outside the cell. Itgbl1 expression was reduced in damaged articular cartilage of OA patients, and ectopic expression of Itgbl1 protected joint cartilage against OA development in a destabilization of the medial meniscus-induced mouse OA model. Co-immunoprecipitation/physical interaction assays, loss/gain-of-function in chondrocytes, Xenopus developmental model, mouse OA model (DMM), recombinant protein treatment Science translational medicine High 30305454
2020 Primary colorectal cancer tumors release ITGBL1-rich extracellular vesicles (EVs) into circulation, which activate resident fibroblasts in remote organs to form pre-metastatic niches. Mechanistically, ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway in fibroblasts, causing them to secrete pro-inflammatory cytokines IL-6 and IL-8 that promote metastatic cancer growth. EV isolation and characterization, in vitro fibroblast activation assays, cytokine measurement (ELISA), NF-κB pathway analysis (Western blot), in vivo mouse metastasis models, loss/gain-of-function Nature communications High 32139701
2015 ITGBL1 knockdown in NSCLC cell lines promotes cancer cell migration and invasion, while recombinant ITGBL1 protein treatment inhibits cell migration and invasion. ITGBL1 acts as a tumor suppressor in NSCLC, and its downregulation is associated with enhanced Wnt/PCP signaling activity. Downregulation of ITGBL1 may result from overexpressed miR-576-5p in NSCLC tissues. siRNA knockdown, recombinant protein treatment, transwell/migration assays, Wnt/PCP signaling pathway analysis Tumour biology Medium 26307393
2016 ITGBL1, as a secreted extracellular matrix protein, promotes ovarian cancer cell migration and adhesion in a concentration-dependent manner (using recombinant protein). ITGBL1 influences the activity of Wnt/PCP signaling and affects the FAK/Src pathway in vitro. Recombinant ITGBL1 protein treatment, transwell/wound healing assays, loss/gain-of-function, Wnt/PCP and FAK/Src pathway analysis Biomedicine & pharmacotherapy Medium 27261588
2019 ITGBL1 promotes EMT, migration, and invasion in prostate cancer via activation of the NF-κB signaling pathway. Upregulation of ITGBL1 enhanced invasion and migration while downregulation showed opposite effects, both in vitro and in vivo. RT-qPCR, Western blot, in vitro migration/invasion assays, NF-κB pathway analysis, in vivo xenograft models OncoTargets and therapy Medium 31190876
2020 ITGBL1 promotes migration and invasion in hepatocellular carcinoma (HCC) cells by stimulating the TGF-β/Smads signaling pathway, along with upregulation of KRT17 and EMT-related genes. ITGBL1 overexpression activated the TGF-β/Smads pathway, while knockout inhibited it. Western blotting, RT-PCR, transwell/wound healing assays, xenograft and orthotopic mouse models, gain/loss-of-function Cell proliferation Medium 32537856
2021 ITGBL1 inhibited NK cell cytotoxicity against melanoma cells, counteracting beneficial effects of anti-PD1 treatment both in vitro and in vivo, functioning as an immunomodulator. Mechanistically, MITF inhibits RUNX2 (an activator of ITGBL1 transcription), and loss of MITF leads to increased RUNX2 activity and upregulation of ITGBL1, promoting immune evasion. Vitamin D3 (an inhibitor of RUNX2) improved melanoma cell killing by immune cells. In vitro NK cytotoxicity assays, anti-PD1 treatment models in vivo, gain/loss-of-function of MITF/RUNX2/ITGBL1, Vitamin D3 treatment Molecular cancer Medium 33413419
2021 ITGBL1 promotes gastric cancer cell proliferation, mobility, and invasion via activation of Akt signaling. Upregulation of ITGBL1 increased phosphorylation of Akt, while silencing ITGBL1 decreased Akt phosphorylation, cell mobility, and proliferation. Western blot for Akt phosphorylation, gain/loss-of-function assays, cell proliferation and migration assays Frontiers in bioscience Medium 33049688
2022 ITGBL1 preferentially inhibits integrin activity at the trailing edge of migrating cells, promoting focal adhesion disassembly there and thus facilitating directional cell migration. ITGBL1-depleted cells showed increased focal adhesions at trailing edges preventing retraction, while ITGBL1 overexpression promoted directional migration by facilitating trailing-edge focal adhesion disassembly. Active forms of integrin, FAK, and Vinculin were specifically detected at trailing edges upon ITGBL1 modulation. siRNA knockdown, ITGBL1 overexpression, wound healing assays, live imaging of membrane-GFP labeled cells, immunostaining for active integrin/FAK/Vinculin Genes & genomics Medium 35066808
2022 Jianpi Jiedu Recipe inhibits CRC metastasis by reducing ITGBL1 levels in CRC-derived EVs, thereby inhibiting ITGBL1-rich EV-mediated activation of cancer-associated fibroblasts through the TNFAIP3-NF-κB signaling pathway, reducing IL-6, IL-8, and α-SMA expression. EV isolation/characterization, Western blot, ELISA, real-time PCR, flow cytometry, in vivo liver metastasis mouse model, immunohistochemistry, immunofluorescence Phytomedicine Medium 35381565
2022 ITGBL1 in small extracellular vesicles derived from dermal fibroblasts promotes fibroblast proliferation, migration, collagen synthesis, and skin thickness in vivo. ITGBL1 protein within SEVs activates the downstream TGF-β1-SMAD2/3 signaling pathway, and overexpression of ITGBL1 increased skin thickness and collagen I content in mouse skin in vivo. LC-MS/MS proteomic analysis of SEVs, in vitro fibroblast functional assays, Western blot for TGF-β1-SMAD2/3, in vivo mouse skin injection model, overexpression assays Journal of nanobiotechnology Medium 35733144
2022 ITGBL1 transcription is suppressed by the transcription factor JDP2 via direct inhibition of the ITGBL1 promoter, as shown by dual-luciferase assay. ITGBL1 activates the TGF-β/Smad pathway to promote pancreatic cancer progression, and overexpression of ITGBL1 reverses the tumor-suppressive effects of JDP2 upregulation. Dual-luciferase reporter assay, gain/loss-of-function, Western blot for TGF-β/Smad pathway, proliferation/migration/invasion assays Brazilian journal of medical and biological research Medium 35584452
2023 Mechanical pressure therapy (PT) reduces scarring by inducing dedifferentiation of myofibroblasts into fibroblasts through the integrin β1/ILK pathway, which inhibits TCF-4, leading to reduced SMYD3 expression; decreased SMYD3 reduces H3K4me3 levels at the ITGBL1 promoter, suppressing ITGBL1 expression. Blocking SMYD3 in animal models reduces scarring, mimicking PT effects. ITGBL1 thus acts as a downstream sensor/mediator of mechanical pressure signals in fibrogenesis. Clinical specimen analysis, ChIP for H3K4me3 at ITGBL1 promoter, Western blot (integrin β1/ILK/TCF-4/SMYD3/ITGBL1 axis), animal scar model with SMYD3 blockade, siRNA knockdown Developmental cell High 37192621
2024 ITGBL1 promotes anoikis resistance and metastasis in gastric cancer through the AKT/Fibulin-2 (FBLN2) axis. ITGBL1 overexpression augments anoikis resistance and metastatic potential, while knockdown suppresses both. Inhibition of AKT/FBLN2 signaling reverses the impact of ITGBL1 on anoikis resistance and metastatic capability. Gain/loss-of-function (overexpression and knockdown), anoikis resistance assays, in vitro migration/invasion assays, in vivo metastasis models, AKT/FBLN2 pathway inhibition Journal of cellular and molecular medicine Medium 38332530
2025 RUNX2 directly binds to the ITGBL1 promoter and enhances its expression, promoting hepatic stellate cell activation and liver fibrosis in HBV infection. Inhibition of RUNX2 with Vitamin D3 or CADD522 significantly reduced ITGBL1 levels and blocked hepatic stellate cell activation. This RUNX2/ITGBL1 pathway is confirmed in both in vitro hepatocyte models and in vivo HBV mouse models. Chromatin immunoprecipitation (ChIP), luciferase reporter assays, Western blotting, in vitro hepatocyte models, in vivo HBV mouse model, pharmacological inhibition of RUNX2 Virology journal High 40287769
2025 RBM15, an m6A methyltransferase, promotes ITGBL1 expression by increasing ITGBL1 mRNA stability through m6A methylation. RBM15-mediated upregulation of ITGBL1 promotes colon adenocarcinoma progression, M2-type macrophage polarization, and CD8+ T cell suppression. These mechanisms were validated by MeRIP and dual-luciferase reporter assay. MeRIP (methylated RNA immunoprecipitation), dual-luciferase reporter assay, RT-qPCR, Western blot, flow cytometry, CCK-8/colony formation/transwell assays, xenograft tumor model The Turkish journal of gastroenterology Medium 39840822
2026 HSP90AB1 interacts with ITGBL1 protein and facilitates its degradation through K63-linked ubiquitination (ubiquitin-proteasome pathway). Downregulation of ITGBL1 in osteosarcoma is partly attributed to abnormal HSP90AB1 upregulation. ITGBL1 activates ER stress by upregulating ROS, thereby triggering autophagy in osteosarcoma cells. Ivermectin was identified as a potent inhibitor of the HSP90AB1-ITGBL1 interaction and inhibited osteosarcoma progression in vivo. Co-immunoprecipitation (Co-IP), virtual drug screening, in vitro and in vivo functional assays, Western blot for ubiquitination and ER stress markers, ROS measurement, autophagy assays Advanced science Medium 41697125
2018 lncITPF, a lncRNA whose fibrotic function depends on its host gene ITGBL1 (they do not share the same promoter and are not co-transcribed), regulates histone H3 and H4 acetylation at the ITGBL1 promoter by targeting heterogeneous nuclear ribonucleoprotein L (hnRNP-L). The upstream inducer of both lncITPF and ITGBL1 in pulmonary fibrosis is TGF-β1-Smad2/3 signaling (Smad2/3 binds to the lncITPF promoter). Note: this finding is primarily about lncITPF regulation OF ITGBL1 expression, not about ITGBL1 protein mechanism per se. RNA-protein pull-down, LC-MS, protein-RNA immunoprecipitation, ChIP-qPCR, CRISPR-Cas9, promoter activity analysis, Northern blot, RACE Molecular therapy Medium 30528088

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer cell 548 19573813
2005 New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS genetics 433 16103914
2020 Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation. Nature communications 224 32139701
2010 Extracellular BMP-antagonist regulation in development and disease: tied up in knots. Trends in cell biology 200 20188563
1996 Rapamycin resistance tied to defective regulation of p27Kip1. Molecular and cellular biology 193 8943329
2013 Discovering causal pathways linking genomic events to transcriptional states using Tied Diffusion Through Interacting Events (TieDIE). Bioinformatics (Oxford, England) 154 23986566
2007 Angiopoietin: a TIE(d) balance in tumor angiogenesis. Molecular cancer research : MCR 127 17634421
2017 Place cells are more strongly tied to landmarks in deep than in superficial CA1. Nature communications 123 28218283
1989 The expression of prothymosin alpha gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation. The Journal of biological chemistry 105 2785990
2017 Polyphosphate granule biogenesis is temporally and functionally tied to cell cycle exit during starvation in Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences of the United States of America 100 28265086
2015 ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFβ Signaling Pathway. Cancer research 86 26060017
2021 Neutrophil Extracellular Traps Tied to Rheumatoid Arthritis: Points to Ponder. Frontiers in immunology 61 33584645
2009 Tie2 is tied at the cell-cell contacts and to extracellular matrix by angiopoietin-1. Experimental & molecular medicine 57 19293632
2018 lncITPF Promotes Pulmonary Fibrosis by Targeting hnRNP-L Depending on Its Host Gene ITGBL1. Molecular therapy : the journal of the American Society of Gene Therapy 49 30528088
2018 ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis. Science translational medicine 48 30305454
2019 Functional and metabolic impairment in cigarette smoke-exposed macrophages is tied to oxidative stress. Scientific reports 47 31270372
2011 Spore formation in Myxococcus xanthus is tied to cytoskeleton functions and polysaccharide spore coat deposition. Molecular microbiology 45 22188356
2009 Tied up in loops: positive and negative autoregulation of p53. Cold Spring Harbor perspectives in biology 44 20452957
1999 Cloning and characterization of a novel beta integrin-related cDNA coding for the protein TIED ("ten beta integrin EGF-like repeat domains") that maps to chromosome band 13q33: A divergent stand-alone integrin stalk structure. Genomics 41 10051402
2020 ITGBL1 promotes cell migration and invasion through stimulating the TGF-β signalling pathway in hepatocellular carcinoma. Cell proliferation 35 32537856
2019 Transcriptomic expression profiling identifies ITGBL1, an epithelial to mesenchymal transition (EMT)-associated gene, is a promising recurrence prediction biomarker in colorectal cancer. Molecular cancer 33 30717807
2016 Extracellular matrix protein ITGBL1 promotes ovarian cancer cell migration and adhesion through Wnt/PCP signaling and FAK/SRC pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 27261588
2004 Sulfide consumption by mussel gill mitochondria is not strictly tied to oxygen reduction: measurements using a novel polarographic sulfide sensor. The Journal of experimental biology 33 15371475
2022 Jianpi Jiedu Recipe inhibits colorectal cancer liver metastasis via regulating ITGBL1-rich extracellular vesicles mediated activation of cancer-associated fibroblasts. Phytomedicine : international journal of phytotherapy and phytopharmacology 32 35381565
2015 Epigenetic downregulated ITGBL1 promotes non-small cell lung cancer cell invasion through Wnt/PCP signaling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 26307393
2013 Supramolecular host-guest pseudocomb conjugates composed of multiple star polycations tied tunably with a linear polycation backbone for gene transfection. Bioconjugate chemistry 30 23682960
2012 Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases. PloS one 30 22970289
2008 Sensory response system of social behavior tied to female reproductive traits. PloS one 29 18852894
2004 Hormone release is tied to changes in cell size in the osmoreceptive prolactin cell of a euryhaline teleost fish, the tilapia, Oreochromis mossambicus. General and comparative endocrinology 28 15242746
2020 An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk. Scientific reports 25 32616758
2022 Tied up in knots: Untangling substrate recognition by the SPOUT methyltransferases. The Journal of biological chemistry 22 35988649
2019 ITGBL1 promotes EMT, invasion and migration by activating NF-κB signaling pathway in prostate cancer. OncoTargets and therapy 20 31190876
2010 Tritopic phenanthroline and pyridine tail-tied aza-scorpiands. Organic & biomolecular chemistry 18 20448894
2021 ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity. Molecular cancer 17 33413419
2022 Small extracellular vesicles derived from dermal fibroblasts promote fibroblast activity and skin development through carrying miR-218 and ITGBL1. Journal of nanobiotechnology 15 35733144
2023 Mechanical pressure-induced dedifferentiation of myofibroblasts inhibits scarring via SMYD3/ITGBL1 signaling. Developmental cell 14 37192621
2019 Three novel genes tied to mandibular prognathism in eastern Mediterranean families. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 14 31256822
2022 Rad1 and Rad10 Tied to Photolyase Regulators Protect Insecticidal Fungal Cells from Solar UV Damage by Photoreactivation. Journal of fungi (Basel, Switzerland) 13 36354891
2022 In toto imaging of early enteric nervous system development reveals that gut colonization is tied to proliferation downstream of Ret. Development (Cambridge, England) 12 36300492
2021 Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors. Frontiers in oncology 12 34745995
2024 ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis. Journal of cellular and molecular medicine 11 38332530
2017 Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding. Biochemistry 11 28876049
2015 Heterogeneous side chain conformation highlights a network of interactions implicated in hysteresis of the knotted protein, minimal tied trefoil. Journal of physics. Condensed matter : an Institute of Physics journal 11 26291198
2011 Tied down: tethering redox proteins to the outer membrane in Neisseria and other genera. Biochemical Society transactions 11 22103547
2020 Regulatory Mechanism of ITGBL1 in the Metastasis of Colorectal Cancer. Frontiers in oncology 9 32211321
2019 Red-Brown Pigmentation of Acidipropionibacterium jensenii Is Tied to Haemolytic Activity and cyl-Like Gene Cluster. Microorganisms 9 31671651
2014 Dioxins contamination in the feed additive (feed grade cupric sulfate) tied to chlorine industry. Scientific reports 8 25102073
2024 Flavonoids regulate LDLR through different mechanisms tied to their specific structures. Journal of lipid research 7 38556050
2020 Evaluation of the Role of ITGBL1 in Ovarian Cancer. Cancers 7 32961775
2010 An RNA end tied to the cell cycle: new ties to apoptosis and microRNA formation? Cell cycle (Georgetown, Tex.) 7 20234174
2024 The pathogenicity of PSEN2 variants is tied to Aβ production and homology to PSEN1. Alzheimer's & dementia : the journal of the Alzheimer's Association 6 39559858
2021 ITGBL1 promotes gastric cancer cell proliferation and invasion via Akt signal pathway. Frontiers in bioscience (Landmark edition) 6 33049688
2025 Aggregate index of systemic inflammation tied to increased fatty liver disease risk: insights from NHANES data. BMC gastroenterology 5 40410700
2023 Changes in dairy cows' behaviour, health, and production after transition from tied to loose housing. Acta veterinaria Scandinavica 4 37391805
2022 ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 4 35584452
2025 Discovery of drug transporter inhibitors tied to long noncoding RNA in resistant cancer cells; a computational model -in silico- study. Frontiers in immunology 3 40352931
2022 Integrin β-like 1 protein (ITGBL1) promotes cell migration by preferentially inhibiting integrin-ECM binding at the trailing edge. Genes & genomics 3 35066808
2020 How autophagy is tied to inflammation and cancer. Molecular & cellular oncology 3 32158928
2020 Treating a Patient with Your Hands Tied: Acute Chest Syndrome in a Jehovah's Witness. Cureus 3 32461845
2010 Drought stress signals in modern and subfossil Quercus laurifolia (Fagaceae) leaves reflect winter precipitation in southern Florida tied to El Nino-Southern Oscillation activity. American journal of botany 3 21622441
2005 Glycoprotein hormones tied but not tethered like other cysteine-knot cytokines. Trends in pharmacological sciences 3 16054241
2025 m6A Methylation Regulator RBM15-Mediated Upregulation of ITGBL1 mRNA Stability Aggravates Colon Adenocarcinoma Progression by Remodeling the Tumor Microenvironment. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 2 39840822
2025 Viremic non-progression in HIV/SIV infection: A tied game between virus and host. Cell reports. Medicine 2 39842407
2025 HBV activates hepatic stellate cells through RUNX2/ITGBL1 axis. Virology journal 2 40287769
2025 Signs of Alzheimer's Disease: Tied to Aging. International journal of molecular sciences 2 40507786
2018 Tied up: Does altering phosphoinositide-mediated membrane trafficking influence neurodegenerative disease phenotypes? Journal of genetics 2 30027907
2025 SOD2 genetics regulating mitochondrial management of oxidative stress is tied to chemical sensitivity in Gulf war veterans. Scientific reports 1 40628885
2025 Coexistence networks of soil methanogens are closely tied to methane generation in wetlands on the northeastern of the Qinghai-Tibet Plateau. Frontiers in microbiology 1 40666798
2025 Grid tied hybrid PV fuel cell system with energy storage and ANFIS based MPPT for smart EV charging. Scientific reports 1 40721927
2024 Welfare assessment traits, milk quantity and quality, and profitability of Anatolian buffalo cows confined in closed-tied or semi-open free-stall barns can be affected by supplementary feeding at milking. Animal bioscience 1 38271965
2024 IP3Rs and nSOCE-Tied Together at Two Ends. Contact (Thousand Oaks (Ventura County, Calif.)) 1 38356482
2023 Enterobacterial common antigen biosynthesis in Yersinia pestis is tied to antimicrobial peptide resistance. bioRxiv : the preprint server for biology 1 37662240
2022 Model spread in tropical low cloud feedback tied to overturning circulation response to warming. Nature communications 1 36402770
2016 The Application of Hem-O-Lok Clips Tied with Threads to Improve Surgical View in Retroperitoneal Laparoscopic Surgery for Renal Cell Carcinoma. Journal of laparoendoscopic & advanced surgical techniques. Part A 1 27575462
2015 Diffuse Large B-cell Lymphoma Classification Tied Up Nicely with a "String". Clinical cancer research : an official journal of the American Association for Cancer Research 1 25829399
1991 [High functional activity of mitochondrial creatine kinase of the myocardium before ischemia is tied with the worst restoration of contractility after reperfusion]. Biulleten' eksperimental'noi biologii i meditsiny 1 1893169
2026 HSP90AB1-Mediated Ubiquitin-Proteasome Degradation of ITGBL1 Promotes Osteosarcoma Progression by Inhibiting Endoplasmic Reticulum Stress-Induced Autophagy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41697125
2026 Evaluating Welfare, Milk Quality and Yield of Rendena Cows in Loose vs. Tied Housing Systems. Animals : an open access journal from MDPI 0 41751097
2026 ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41806112
2026 Stress Responses Tied to Metastasis and Immune Evasion. Cancer discovery 0 41894698
2026 1H, 13C, 15N backbone assignment of the minimally tied trefoil knot, MTTSA, a 23s rRNA SPOUT methyltransferase. Biomolecular NMR assignments 0 41963736
2026 Spring-Summer Caribbean Sea marine heatwaves tied to previous Winter Indian Ocean marine heatwaves. Nature communications 0 42156727
2025 An amino acid polymorphism in the membrane progesterone receptor alpha protein is tied to female sexual maturity in the large yellow croaker (Larimichthys crocea). Gene 0 40064306
2025 In anaerobic reactors the microbial community structure depends on feed type, with no "keystone" species tied to COD removal. Frontiers in microbiology 0 40438221
2025 Chromosome 21 variants tied to severe asthma exacerbations: A genome-wide association study in a Brazilian population. The journal of allergy and clinical immunology. Global 0 40677615
2025 Design of an intelligent AI-based multi-layer optimization framework for grid-tied solar PV-fuel cell hybrid energy systems. MethodsX 0 40822542
2025 A Neural-Glial Model of the ApoE-SORT1-FABP7 Axis Tied to Sleep Disruption and Alzheimer's Disease Pathophysiology. Biomolecules 0 41154661
2025 Variant in a Taste Receptor Locus Tied to Changes in the Use of Insomnia Medication. Biological psychiatry global open science 0 41492454
2025 Glioma chemotherapeutic resistance is tied to membrane electrophysiological properties and glycosylation. Bioengineering & translational medicine 0 41573377
2024 Sacrificed Maya boys tied to myth of 'Hero Twins'. Science (New York, N.Y.) 0 38870299
2023 Drivers of Differential Time to Diagnosis in Pediatric ALL Tied to Race and Ethnicity. Journal of pediatric hematology/oncology 0 37526394
2013 A short note on how tied fights affect cortisol levels. Integrative zoology 0 24020471

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