{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:10:24Z","timestamp":1790359824764,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,9]],"date-time":"2019-11-09T00:00:00Z","timestamp":1573257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The relationship between epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways in tumor growth is well established. EGF induces VEGF production in cancer cells, and the paracrine VEGF activates vascular endothelial cells to promote tumor angiogenesis and thus supports tumor cell growth in an angiogenesis-dependent manner. In this study, we found angiogenesis-independent novel crosstalk between the VEGF and the EGF pathways in the regulation of colon cancer cell proliferation. Stimulation of colon cancer cells with VEGF-A and placental growth factor (PlGF) activated VEGF receptor-1 (VEGFR-1) and increased proliferation activity in an autocrine EGF\/EGF receptor (EGF-R)-dependent manner. Mechanistically, VEGFR-1 interacted with and stabilized EGF-R, leading to increased EGF-R protein levels and prolonged its expression on cell surface plasma membrane. In contrast, VEGFR-1 blockade by a neutralizing antibody and an antagonistic peptide of VEGFR-1 suppressed the complex formation of VEGFR-1 and EGF-R and decreased EGF-R expression via a lysosome-dependent pathway, resulting in the suppression of proliferation activity. Our results indicated that VEGFR-1 regulated EGF-R expression to promote proliferation activity in a cell-autonomous-dependent manner.<\/jats:p>","DOI":"10.3390\/ijms20225608","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T04:07:07Z","timestamp":1573531627000},"page":"5608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells"],"prefix":"10.3390","volume":"20","author":[{"given":"Hikaru","family":"Nagano","sequence":"first","affiliation":[{"name":"Department of Medical Nutrition, Osaka Prefecture University, 3-7-30 Habikino, Habikino, Osaka 583-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Tomida","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Faculty of Home Economics, Tokyo Kasei University, 1-18-1 Kaga, Itabashi, Tokyo 173-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigetada","family":"Teshima-Kondo","sequence":"additional","affiliation":[{"name":"Department of Medical Nutrition, Osaka Prefecture University, 3-7-30 Habikino, Habikino, Osaka 583-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in Signaling and Disease: Beyond Discovery and Development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mercurio, A. 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