@article{93c236e8a59e44a78d3a85d152fe4086,
title = "Targeting the cyclin-dependent kinase 5 in metastatic melanoma",
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.",
keywords = "CDK5, Cyclin-dependent kinases, Metastasis, Mouse cancer models",
author = "Samanta Sharma and Tian Zhang and Wojciech Michowski and Rebecca, {Vito W.} and Min Xiao and Roberta Ferretti and Suski, {Jan M.} and Bronson, {Roderick T.} and Paulo, {Joao A.} and Dennie Frederick and Anne Fassl and Boland, {Genevieve M.} and Yan Geng and Lees, {Jacqueline A.} and Medema, {Rene H.} and Meenhard Herlyn and Gygi, {Steven P.} and Piotr Sicinski",
note = "Funding Information: Author contributions: S.S., W.M., and P.S. designed research; S.S., T.Z., W.M., V.W.R., M.X., J.M.S., A.F., Y.G., and P.S. performed research; R.F., J.A.P., D.F., G.M.B., and J.A.L. contributed new reagents/analytic tools; S.S., R.T.B., Y.G., R.H.M., M.H., S.P.G., and P.S. analyzed data; and S.S. and P.S. wrote the paper. Competing interest statement: P.S. has been a consultant at Novartis, Genovis, Guide-point, The Planning Shop, ORIC Pharmaceuticals, and Exo Therapeutics; his laboratory receives research funding from Novartis. W.M. is currently an employee of Cedilla Therapeutics. This article is a PNAS Direct Submission. R.M. is a guest editor invited by the Editorial Board. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = apr,
day = "7",
doi = "10.1073/pnas.1912617117",
language = "English (US)",
volume = "117",
pages = "8001--8012",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "14",
}