ArticleThe Journal of biological chemistry2013
An integrin binding-defective mutant of insulin-like growth factor-1 (R36E/R37E IGF1) acts as a dominant-negative antagonist of the IGF1 receptor (IGF1R) and suppresses tumorigenesis but still binds to IGF1R.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- New insights on the cardiovascular effects of IGF-1.Frontiers in endocrinology · 2023Pooled it
- IGF1 Binding to Integrin αvβ3 Induces Direct Gα13 Binding to IGF1R Kinase.International journal of molecular sciences · 2026Article
- Galectin-3 Binds to the Allosteric Site and Activates Integrins αvβ3, αIIbβ3, and α5β1, and Lactose Inhibits This Activation.Biomolecules · 2026Article
- Article
- Article
- The heparin-binding domain of VEGF165 directly binds to integrin αvβ3 and VEGFR2/KDR D1: a potential mechanism of negative regulation of VEGF165 signaling by αvβ3.Frontiers in cell and developmental biology · 2024Article
- Review
- Review
- Recombinant Insulin-Like Growth Factor 1 Dimers: Receptor Binding Affinities and Activation Abilities.International journal of peptide research and therapeutics · 2023Article
- Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells.Cancer science · 2022Article
- A viral insulin-like peptide is a natural competitive antagonist of the human IGF-1 receptor.Molecular metabolism · 2021Article
- Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation.International journal of molecular sciences · 2020Review
- Niche Modulation of IGF-1R Signaling: Its Role in Stem Cell Pluripotency, Cancer Reprogramming, and Therapeutic Applications.Frontiers in cell and developmental biology · 2020Review
- Therapeutic Targeting of the IGF Axis.Cells · 2019Review
- Insulin Stimulates PI3K/AKT and Cell Adhesion to Promote the Survival of Individualized Human Embryonic Stem Cells.Stem cells (Dayton, Ohio) · 2019Article
- Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer.Cancers · 2019Review
- Roles of EphA1/A2 and ephrin-A1 in cancer.Cancer science · 2019Review
- Direct binding to integrins and loss of disulfide linkage in interleukin-1β (IL-1β) are involved in the agonistic action of IL-1β.The Journal of biological chemistry · 2017Article
- The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis.Bioscience reports · 2017Article
- Crosstalk between insulin-like growth factor (IGF) receptor and integrins through direct integrin binding to IGF1.Cytokine & growth factor reviews · 2017Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor-1 (IGF1) is a major therapeutic target for cancer. We recently reported that IGF1 directly binds to integrins (αvβ3 and α6β4) and induces ternary complex formation (integrin-IGF1-IGF1 receptor (IGF1R)) and that the integrin binding-defective mutant of IGF1 (R36E/R37E) is defective in signaling and ternary complex formation. These findings predict that R36E/R37E competes with WT IGF1 for binding to IGF1R and inhibits IGF signaling. Here, we described that excess R36E/R37E suppressed cell viability increased by WT IGF1 in vitro in non-transformed cells. We studied the effect of R36E/R37E on viability and tumorigenesis in cancer cell lines. We did not detect an effect of WT IGF1 or R36E/R37E in cancer cells under anchorage-dependent conditions. However, under anchorage-independent conditions, WT IGF1 enhanced cell viability and induced signals, whereas R36E/R37E did not. Notably, excess R36E/R37E suppressed cell viability and signaling induced by WT IGF1 under anchorage-independent conditions. Using cancer cells stably expressing WT IGF1 or R36E/R37E, we determined that R36E/R37E suppressed tumorigenesis in vivo, whereas WT IGF1 markedly enhanced it. R36E/R37E suppressed the binding of WT IGF1 to the cell surface and the subsequent ternary complex formation induced by WT IGF1. R36E/R37E suppressed activation of IGF1R by insulin. WT IGF1, but not R36E/R37E, induced ternary complex formation with the IGF1R/insulin receptor hybrid. These findings suggest that 1) IGF1 induces signals under anchorage-independent conditions and that 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.