{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T10:43:17Z","timestamp":1787395397754,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T00:00:00Z","timestamp":1574467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2017\u2014ID"],"award-info":[{"award-number":["IG 2017\u2014ID"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The vascular endothelial growth factor receptor\u20101 (VEGFR\u20101) is a tyrosine kinase receptor frequently expressed in melanoma. Its activation by VEGF\u2010A or placental growth factor (PlGF) promotes tumour cell survival, migration and invasiveness. Moreover, VEGFR\u20101 stimulation contributes to pathological angiogenesis and induces recruitment of tumour\u2010associated macrophages. Since melanoma acquired resistance to BRAF inhibitors (BRAFi) has been associated with activation of pro\u2010angiogenic pathways, we have investigated VEGFR\u20101 involvement in vemurafenib resistance. Results indicate that human melanoma cells rendered resistant to vemurafenib secrete greater amounts of VEGF\u2010A and express higher VEGFR\u20101 levels compared with their BRAFi\u2010sensitive counterparts. Transient VEGFR\u20101 silencing in susceptible melanoma cells delays resistance development, whereas in resistant cells it increases sensitivity to the BRAFi. Consistently, enforced VEGFR\u20101 expression, by stable gene transfection in receptor\u2010negative melanoma cells, markedly reduces sensitivity to vemurafenib. Moreover, melanoma cells expressing VEGFR\u20101 are more invasive than VEGFR\u20101 deficient cells and receptor blockade by a specific monoclonal antibody (D16F7 mAb) reduces extracellular matrix invasion triggered by VEGF\u2010A and PlGF. These data suggest that VEGFR\u20101 up\u2010regulation might contribute to melanoma progression and spreading after acquisition of a drug\u2010resistant phenotype. Thus, VEGFR\u20101 inhibition with D16F7 mAb might be a suitable adjunct therapy for VEGFR\u20101 positive tumours with acquired resistance to vemurafenib.<\/jats:p>","DOI":"10.1111\/jcmm.14755","type":"journal-article","created":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T08:40:32Z","timestamp":1574498432000},"page":"465-475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Role of VEGFR\u20101 in melanoma acquired resistance to the BRAF inhibitor vemurafenib"],"prefix":"10.1111","volume":"24","author":[{"given":"Maria Grazia","family":"Atzori","sequence":"first","affiliation":[{"name":"Department of Systems Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ceci","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine University of Rome Tor Vergata Rome 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