Title: Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells.

Authors: Coles, Garry L; Cristea, Sandra; Webber, James T; Levin, Rebecca S; Moss, Steven M; He, Andy; Sangodkar, Jaya; Hwang, Yeonjoo C; Arand, Julia; Drainas, Alexandros P; Mooney, Nancie A; Demeter, Janos; Spradlin, Jessica N; Mauch, Brandon; Le, Vicky; Shue, Yan Ting; Ko, Julie H; Lee, Myung Chang; Kong, Christina; Nomura, Daniel K; Ohlmeyer, Michael; Swaney, Danielle L; Krogan, Nevan J; Jackson, Peter K; Narla, Goutham; Gordan, John D; Shokat, Kevan M; Sage, Julien

Published In Cancer Cell, (2020 07 13)

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.

PubMed ID: 32531271

MeSH Terms: No MeSH terms associated with this publication