| Literature DB >> 32531271 |
Garry L Coles1, Sandra Cristea1, James T Webber2, Rebecca S Levin3, Steven M Moss4, Andy He1, Jaya Sangodkar5, Yeonjoo C Hwang6, Julia Arand1, Alexandros P Drainas1, Nancie A Mooney7, Janos Demeter7, Jessica N Spradlin8, Brandon Mauch1, Vicky Le1, Yan Ting Shue1, Julie H Ko1, Myung Chang Lee1, Christina Kong9, Daniel K Nomura10, Michael Ohlmeyer11, Danielle L Swaney12, Nevan J Krogan12, Peter K Jackson13, Goutham Narla5, John D Gordan14, Kevan M Shokat3, Julien Sage15.
Abstract
Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many PKA substrates and mechanisms of action. In particular, PKA activity is required for the propagation of SCLC stem cells in transplantation studies. Broad proteomic analysis of recalcitrant cancers has the potential to uncover targetable signaling networks, such as the GNAS/PKA/PP2A axis in SCLC.Entities:
Keywords: GNAS; PKA; PP2A; SCLC; cancer; cancer stem cells; kinase; lung; neuroendocrine; phosphatase; proteomics
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Year: 2020 PMID： 32531271 PMCID： PMC7363571 DOI： 10.1016/j.ccell.2020.05.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743