{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:25:48Z","timestamp":1772252748882,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["NCI P30CA093373"],"award-info":[{"award-number":["NCI P30CA093373"]}]},{"name":"Department of Dermatology","award":["NCI P30CA093373"],"award-info":[{"award-number":["NCI P30CA093373"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>FGF9 is a potent mitogen and survival factor, but FGF9 protein levels are generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in cancer. However, the mechanism of FGF9 action has not been fully established. Previous studies showed that FGF1 and FGF2 directly bind to integrin \u03b1v\u03b23, and this interaction is critical for signaling functions (FGF\u2013integrin crosstalk). FGF1 and FGF2 mutants defective in integrin binding were defective in signaling, whereas the mutants still bound to FGFR suppressed angiogenesis and tumor growth, indicating that they act as antagonists. We hypothesize that FGF9 requires direct integrin binding for signaling. Here, we show that docking simulation of the interaction between FGF9 and \u03b1v\u03b23 predicted that FGF9 binds to the classical ligand-binding site of \u03b1v\u03b23. We show that FGF9 bound to integrin \u03b1v\u03b23 and generated FGF9 mutants in the predicted integrin-binding interface. An FGF9 mutant (R108E) was defective in integrin binding, activating FRS2\u03b1 and ERK1\/2, inducing DNA synthesis, cancer cell migration, and invasion in vitro. R108E suppressed DNA synthesis and activation of FRS2\u03b1 and ERK1\/2 induced by WT FGF9 (dominant-negative effect). These findings indicate that FGF9 requires direct integrin binding for signaling and that R108E has potential as an antagonist to FGF9 signaling.<\/jats:p>","DOI":"10.3390\/cells13040307","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:12:58Z","timestamp":1707286378000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["FGF9, a Potent Mitogen, Is a New Ligand for Integrin \u03b1v\u03b23, and the FGF9 Mutant Defective in Integrin Binding Acts as an Antagonist"],"prefix":"10.3390","volume":"13","author":[{"given":"Chih-Chieh","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko K.","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-6630","authenticated-orcid":false,"given":"Chao-Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukina","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Science, Morinomiya University of Medical Sciences, Osaka 536-0025, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Science, Morinomiya University of Medical Sciences, Osaka 536-0025, Japan"},{"name":"Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5481-9589","authenticated-orcid":false,"given":"Yoshikazu","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Takada, Y., Ye, X., and Simon, S. 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