{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:48:20Z","timestamp":1785775700234,"version":"3.56.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2023AFB498"],"award-info":[{"award-number":["2023AFB498"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Clear cell renal cell carcinoma (ccRCC) is a highly aggressive malignancy with limited treatment options. Although RASD2, which encodes a Ras\u2010related GTP\u2010binding protein, has been linked to melanoma progression, its role in ccRCC remains unclear. In this study, we systematically investigated the oncogenic functions and mechanisms of RASD2 in ccRCC. Clinically, RASD2 was significantly overexpressed in tumor tissues compared with adjacent normal tissues and correlated with poor patient prognosis. Functional studies demonstrated that RASD2 promotes proliferation, migration, and invasion of the ccRCC cells in\u00a0vitro, findings further supported by xenograft models in nude mice. Mechanistically, RASD2 activated the P38\/ERK\u2013MAPK pathway, and inhibition experiments confirmed its necessity for RASD2\u2010driven oncogenesis. Through co\u2010immunoprecipitation and LC\u2013MS\/MS, we identified RAF1 as a key binding partner. RASD2 enhanced RAF1 phosphorylation at Ser338, thereby activating the P38\/ERK\u2013MAPK pathway. RAF1 phosphorylation at Ser338 was critical for ccRCC cell growth, migration, and invasion. The RAF1 inhibitor BAY43\u20109006 reduced p\u2010RAF1 (Ser338)\/RAF1 levels, suppressed ccRCC proliferation, migration, and invasion in\u00a0vitro, and significantly inhibited tumor growth in\u00a0vivo. These findings identify RASD2 as a novel oncoprotein that promotes ccRCC tumorigenesis through p\u2010RAF1 (Ser338)\u2010mediated P38\/ERK\u2013MAPK activation, suggesting RAF1 inhibition as a promising therapeutic strategy for ccRCC patients.<\/jats:p>","DOI":"10.1111\/cas.70415","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:45:19Z","timestamp":1780382719000},"page":"2194-2207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RASD<\/scp>\n                    2 Drives Renal Clear Cell Carcinoma Progression via\n                    <scp>RAF<\/scp>\n                    1 (Ser338) Phosphorylation"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2670-3351","authenticated-orcid":false,"given":"Jingxuan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Urology, Postgraduate Union Training Base of General Hospital of Central Theater Command, School of Medicine Wuhan University of Science and Technology  Wuhan Hubei China"},{"name":"Department of Urology General Hospital of Central Theater Command of Chinese People's Liberation Army  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yu","sequence":"additional","affiliation":[{"name":"Xianning Central Hospital The First Affiliated Hospital of Hubei University of Science and Technology  Xianning Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Southwest Hospital, Army Medical University (Third Military Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Urology, Postgraduate Union Training Base of General Hospital of Central Theater Command, School of Medicine Wuhan University 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