| Literature DB >> 32193336 |
Samanta Sharma1,2, Tian Zhang3, Wojciech Michowski1,2, Vito W Rebecca4, Min Xiao4, Roberta Ferretti5,6, Jan M Suski1,2, Roderick T Bronson7, Joao A Paulo3, Dennie Frederick8, Anne Fassl1,2, Genevieve M Boland8, Yan Geng1,2, Jacqueline A Lees5,9, Rene H Medema10, Meenhard Herlyn4, Steven P Gygi3, Piotr Sicinski11,2.
Abstract
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.Entities:
Keywords: CDK5; cyclin-dependent kinases; metastasis; mouse cancer models
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Year: 2020 PMID： 32193336 PMCID： PMC7149478 DOI： 10.1073/pnas.1912617117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205