{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:45:52Z","timestamp":1760150752745,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004099","name":"French League Against Cancer","doi-asserted-by":"publisher","award":["EL2015.LNCC\/SaC"],"award-info":[{"award-number":["EL2015.LNCC\/SaC"]}],"id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>von Hippel-Lindau (VHL) disease, due to mutations of the tumor suppressor VHL gene, is a rare hereditary syndrome with a high risk of developing clear cell renal cell carcinoma (ccRCC). We asked whether the VHL-C162F mutation interferes with proliferation, migration, healing and forming colony ability by using wild-type VHL (WT VHL) and VHL-C162F reconstituted cells. We then analyzed the in vitro impact of the sunitinib treatment on VHL-C162F cells. We showed that VHL-C162F mutations have no impact on cell morphology, colony formation and migration ability but confer a significant higher healing ability than in WT VHL cells. RNA sequencing analysis revealed that VHL-C162F mutation upregulates genes involved in hypoxia and epithelial mesenchymal transition (EMT) pathways by comparison with VHL WT cells. We next showed a decrease in healing ability in VHL-C162F cells depleting on ZHX2, an oncogenic driver of ccRCC, highlighting the potential involvement of ZHX2 in aggressiveness of the VHL-C162F cells. Moreover, we found that sunitinib treatment inhibits ZHX2 expression and induces a reduced proliferation correlating with downregulation of P-ERK. Sunitinib treatment also conferred a more mesenchymal profile to VHL-C162F cells with significant downregulation of E-cadherin and upregulation of N-cadherin, Slug and AXL. Sunitinib therapy may therefore promote disease progression in VHL-C162F patients.<\/jats:p>","DOI":"10.3390\/cancers16010034","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T07:20:31Z","timestamp":1703056831000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sunitinib Treatment of VHL C162F Cells Slows Down Proliferation and Healing Ability via Downregulation of ZHX2 and Confers a Mesenchymal Phenotype"],"prefix":"10.3390","volume":"16","author":[{"given":"St\u00e9phanie","family":"Buart","sequence":"first","affiliation":[{"name":"INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculty of Medicine, University Paris-Saclay, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u2019boyba Khadija","family":"Diop","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, University of Paris-Saclay, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-6027","authenticated-orcid":false,"given":"Isabelle","family":"Damei","sequence":"additional","affiliation":[{"name":"INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculty of Medicine, University Paris-Saclay, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salem","family":"Chouaib","sequence":"additional","affiliation":[{"name":"INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculty of Medicine, University Paris-Saclay, 94805 Villejuif, France"},{"name":"Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman 4184, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1097\/MPA.0000000000000875","article-title":"Clinical Profile of Pancreatic Cystic Lesions in von Hippel-Lindau Disease: A Series of 48 Patients Seen at a Tertiary Institution","volume":"46","author":"Sharma","year":"2017","journal-title":"Pancreas"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1586\/14737140.8.1.63","article-title":"VHL inactivation in renal cell carcinoma: Implications for diagnosis, prognosis and treatment","volume":"8","author":"Rathmell","year":"2008","journal-title":"Expert Rev. 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