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Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss.
Liu, Xijuan; Simon, Jeremy M; Xie, Haibiao; Hu, Lianxin; Wang, Jun; Zurlo, Giada; Fan, Cheng; Ptacek, Travis S; Herring, Laura; Tan, Xianming; Li, Mingjie; Baldwin, Albert S; Kim, William Y; Wu, Tao; Kirschner, Marc W; Gong, Kan; Zhang, Qing.
Afiliación
  • Liu X; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Simon JM; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Xie H; Department of Urology, Peking University First Hospital, Beijing, China.
  • Hu L; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • Wang J; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Zurlo G; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • Fan C; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Ptacek TS; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Herring L; Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; UNC Proteomics Core Facility, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Tan X; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Li M; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • Baldwin AS; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Kim WY; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Wu T; Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
  • Kirschner MW; Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
  • Gong K; Department of Urology, Peking University First Hospital, Beijing, China.
  • Zhang Q; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, U
Mol Cell ; 77(6): 1294-1306.e5, 2020 03 19.
Article en En | MEDLINE | ID: mdl-32023483
von Hippel-Lindau (VHL) is a critical tumor suppressor in clear cell renal cell carcinomas (ccRCCs). It is important to identify additional therapeutic targets in ccRCC downstream of VHL loss besides hypoxia-inducible factor 2α (HIF2α). By performing a genome-wide screen, we identified Scm-like with four malignant brain tumor domains 1 (SFMBT1) as a candidate pVHL target. SFMBT1 was considered to be a transcriptional repressor but its role in cancer remains unclear. ccRCC patients with VHL loss-of-function mutations displayed elevated SFMBT1 protein levels. SFMBT1 hydroxylation on Proline residue 651 by EglN1 mediated its ubiquitination and degradation governed by pVHL. Depletion of SFMBT1 abolished ccRCC cell proliferation in vitro and inhibited orthotopic tumor growth in vivo. Integrated analyses of ChIP-seq, RNA-seq, and patient prognosis identified sphingosine kinase 1 (SPHK1) as a key SFMBT1 target gene contributing to its oncogenic phenotype. Therefore, the pVHL-SFMBT1-SPHK1 axis serves as a potential therapeutic avenue for ccRCC.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteínas Represoras / Carcinoma de Células Renales / Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / Fosfotransferasas (Aceptor de Grupo Alcohol) / Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau / Neoplasias Renales Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteínas Represoras / Carcinoma de Células Renales / Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / Fosfotransferasas (Aceptor de Grupo Alcohol) / Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau / Neoplasias Renales Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos