| Literature DB >> 29444439 |
Tina L Yuan1, Arnaud Amzallag2, Rachel Bagni3, Ming Yi3, Shervin Afghani1, William Burgan3, Nicole Fer3, Leslie A Strathern3, Katie Powell3, Brian Smith3, Andrew M Waters3, David Drubin4, Ty Thomson4, Rosy Liao5, Patricia Greninger2, Giovanna T Stein2, Ellen Murchie2, Eliane Cortez2, Regina K Egan2, Lauren Procter3, Matthew Bess3, Kwong Tai Cheng3, Chih-Shia Lee6, Liam Changwoo Lee6, Christof Fellmann7, Robert Stephens3, Ji Luo6, Scott W Lowe8, Cyril H Benes9, Frank McCormick10.
Abstract
KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention.Entities:
Keywords: KRAS; RNAi screen; RSK; paralogs; redundancy
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Year: 2018 PMID： 29444439 PMCID： PMC6343826 DOI： 10.1016/j.celrep.2018.01.051
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423