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The SUMO protease SENP1 promotes aggressive behaviors of high HIF2α expressing renal cell carcinoma cells.
Lee, Moon Hee; Sung, Kyung; Beebe, David; Huang, Wei; Shapiro, Dan; Miyamoto, Shigeki; Abel, E Jason.
Afiliación
  • Lee MH; Department of Urology, University of Wisconsin-Madison, Madison, WI, 53705, USA.
  • Sung K; Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, the U.S. FDA, White Oak, MD, 20993, USA.
  • Beebe D; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53705, USA.
  • Huang W; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53705, USA.
  • Shapiro D; University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA.
  • Miyamoto S; University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA.
  • Abel EJ; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Oncogenesis ; 11(1): 65, 2022 Oct 25.
Article en En | MEDLINE | ID: mdl-36284084
While an important role for the SUMO protease SENP1 is recognized in multiple solid cancers, its role in renal cell carcinoma (RCC) pathogenesis, particularly the most dominant subtype, clear cell RCC (ccRCC), is poorly understood. Here we show that a combination of high HIF2α and SENP1 expression in ccRCC samples predicts poor patient survival. Using ccRCC cell models that express high HIF2α but low SENP1, we show that overexpression of SENP1 reduces sumoylation and ubiquitination of HIF2α, increases HIF2α transcriptional activity, and enhances expression of genes associated with cancer cell invasion, stemness and epithelial-mesenchymal transition. Accordingly, ccRCC cells with high HIF2α and SENP1 showed increased invasion and sphere formation in vitro, and local invasion and metastasis in vivo. Finally, SENP1 overexpression caused high HIF2α ccRCC cells to acquire resistance to a clinical mTOR inhibitor, everolimus. These results reveal a combination of high SENP1 and HIF2α expression gives particularly poor prognosis for ccRCC patients and suggest that SENP1 may be an attractive new target for treating metastatic RCC (mRCC).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Oncogenesis Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Oncogenesis Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos