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USP21 deubiquitinase elevates macropinocytosis to enable oncogenic KRAS bypass in pancreatic cancer.
Hou, Pingping; Ma, Xingdi; Yang, Zecheng; Zhang, Qiang; Wu, Chang-Jiun; Li, Jun; Tan, Lin; Yao, Wantong; Yan, Liang; Zhou, Xin; Kimmelman, Alec C; Lorenzi, Philip L; Zhang, Jianhua; Jiang, Shan; Spring, Denise; Wang, Y Alan; DePinho, Ronald A.
Afiliación
  • Hou P; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Ma X; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Yang Z; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Zhang Q; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Wu CJ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Li J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Tan L; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Yao W; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Yan L; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Zhou X; Cancer Research Institute of Jilin University, The First Hospital of Jilin University, ChangChun 130061, China.
  • Kimmelman AC; Perlmutter Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
  • Lorenzi PL; Department of Radiation Oncology, New York University School of Medicine, New York, New York 10016, USA.
  • Zhang J; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Jiang S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Spring D; Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Wang YA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • DePinho RA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Genes Dev ; 35(19-20): 1327-1332, 2021 10 01.
Article en En | MEDLINE | ID: mdl-34531315
Activating mutations in KRAS (KRAS*) are present in nearly all pancreatic ductal adenocarcinoma (PDAC) cases and critical for tumor maintenance. By using an inducible KRAS* PDAC mouse model, we identified a deubiquitinase USP21-driven resistance mechanism to anti-KRAS* therapy. USP21 promotes KRAS*-independent tumor growth via its regulation of MARK3-induced macropinocytosis, which serves to maintain intracellular amino acid levels for anabolic growth. The USP21-mediated KRAS* bypass, coupled with the frequent amplification of USP21 in human PDAC tumors, encourages the assessment of USP21 as a novel drug target as well as a potential parameter that may affect responsiveness to emergent anti-KRAS* therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Límite: Animals Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Límite: Animals Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos