ArticleThe Journal of biological chemistry2016
GIV/Girdin (Gα-interacting, Vesicle-associated Protein/Girdin) Creates a Positive Feedback Loop That Potentiates Outside-in Integrin Signaling in Cancer Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Shared Genetic Architecture and Pleiotropic Loci Linking Endometriosis and Inflammatory Bowel Disease: An Integrative GWAS, Colocalization, and Mendelian Randomization Study.BioMed research international · 2026Article
- Girdin silencing enhances mebendazole-mediated anticancer activity: a combinatorial therapeutic strategy for ovarian cancer.Medical oncology (Northwood, London, England) · 2025Article
- Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif.The Journal of biological chemistry · 2024Review
- Girdin regulates both migration and angiogenesis in pancreatic cancer cell lines.Oncology reports · 2023Article
- Small-molecule targeting of GPCR-independent noncanonical G-protein signaling in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells.International journal of molecular sciences · 2021Article
- Article
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- GIV/Girdin and Exo70 Collaboratively Regulate the Mammalian Polarized Exocytic Machinery.iScience · 2020Article
- The DISC1-Girdin complex - a missing link in signaling to the T cell cytoskeleton.Journal of cell science · 2020Article
- GIV•Kindlin Interaction Is Required for Kindlin-Mediated Integrin Recognition and Activation.iScience · 2020Article
- Cell Migration in Microfabricated 3D Collagen Microtracks is Mediated through the Prometastatic Protein Girdin.Cellular and molecular bioengineering · 2018Article
- Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Gαi-GIV binding interface is a druggable protein-protein interaction.Scientific reports · 2017Article
- Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression.Convergent science physical oncology · 2017Article
- Membrane Recruitment of the Non-receptor Protein GIV/Girdin (Gα-interacting, Vesicle-associated Protein/Girdin) Is Sufficient for Activating Heterotrimeric G Protein Signaling.The Journal of biological chemistry · 2016Article
- Biochemical, Biophysical and Cellular Techniques to Study the Guanine Nucleotide Exchange Factor, GIV/Girdin.Current protocols in chemical biology · 2016Article
- Hint1 suppresses migration and invasion of hepatocellular carcinoma cells in vitro by modulating girdin activity.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the tyrosine kinase focal adhesion kinase (FAK) upon cell stimulation by the extracellular matrix initiates integrin outside-in signaling. FAK is directly recruited to active integrins, which enhances its kinase activity and triggers downstream signaling like activation of PI3K. We recently described that Gα-interacting, vesicle-associated protein (GIV), a protein up-regulated in metastatic cancers, is also required for outside-in integrin signaling. More specifically, we found that GIV is a non-receptor guanine nucleotide exchange factor that activates trimeric G proteins in response to integrin stimulation to enhance PI3K signaling and tumor cell migration. In contrast, previous reports have established that GIV is involved in phosphotyrosine (Tyr(P))-based signaling in response to growth factor stimulation;i.e.GIV phosphorylation at Tyr-1764 and Tyr-1798 recruits and activates PI3K. Here we show that phosphorylation of GIV at Tyr-1764/Tyr-1798 is also required to enhance PI3K-Akt signaling and tumor cell migration in response to integrin stimulation, indicating that GIV functions in Tyr(P)-dependent integrin signaling. Unexpectedly, we found that activation of FAK, an upstream component of the integrin Tyr(P) signaling cascade, was diminished in GIV-depleted cells, suggesting that GIV is required to establish a positive feedback loop that enhances integrin-FAK signaling. Mechanistically, we demonstrate that this feedback activation of FAK depends on both guanine nucleotide exchange factor and Tyr(P) GIV signaling as well as on their convergence point, PI3K. Taken together, our results provide novel mechanistic insights into how GIV promotes proinvasive cancer cell behavior by working as a signal-amplifying platform at the crossroads of trimeric G protein and Tyr(P) signaling.
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Registered trials
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