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Targeting the cyclin-dependent kinase 5 in metastatic melanoma.
Sharma, Samanta; Zhang, Tian; Michowski, Wojciech; Rebecca, Vito W; Xiao, Min; Ferretti, Roberta; Suski, Jan M; Bronson, Roderick T; Paulo, Joao A; Frederick, Dennie; Fassl, Anne; Boland, Genevieve M; Geng, Yan; Lees, Jacqueline A; Medema, Rene H; Herlyn, Meenhard; Gygi, Steven P; Sicinski, Piotr.
Afiliación
  • Sharma S; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
  • Zhang T; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
  • Michowski W; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Rebecca VW; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
  • Xiao M; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
  • Ferretti R; Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104.
  • Suski JM; Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104.
  • Bronson RT; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Paulo JA; Translational Innovation Platform Oncology, Emmanuel Merck Darmstadt (EMD) Serono Research and Development Institute, Inc., Billerica, MA 01821.
  • Frederick D; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
  • Fassl A; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
  • Boland GM; Rodent Histopathology Core, Harvard Medical School, Boston, MA 02115.
  • Geng Y; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Lees JA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
  • Medema RH; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
  • Herlyn M; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
  • Gygi SP; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
  • Sicinski P; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
Proc Natl Acad Sci U S A ; 117(14): 8001-8012, 2020 04 07.
Article en En | MEDLINE | ID: mdl-32193336
The cyclin-dependent kinase 5 (CDK5), originally described as a neuronal-specific kinase, is also frequently activated in human cancers. Using conditional CDK5 knockout mice and a mouse model of highly metastatic melanoma, we found that CDK5 is dispensable for the growth of primary tumors. However, we observed that ablation of CDK5 completely abrogated the metastasis, revealing that CDK5 is essential for the metastatic spread. In mouse and human melanoma cells CDK5 promotes cell invasiveness by directly phosphorylating an intermediate filament protein, vimentin, thereby inhibiting assembly of vimentin filaments. Chemical inhibition of CDK5 blocks the metastatic spread of patient-derived melanomas in patient-derived xenograft (PDX) mouse models. Hence, inhibition of CDK5 might represent a very potent therapeutic strategy to impede the metastatic dissemination of malignant cells.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Melanoma Experimental / Quinasa 5 Dependiente de la Ciclina / Melanoma Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Melanoma Experimental / Quinasa 5 Dependiente de la Ciclina / Melanoma Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article