KRAS and YAP1 converge to regulate EMT and tumor survival.
KRAS and YAP1 converge to regulate EMT and tumor survival.
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DOI：
10.1016/j.cell.2014.06.004
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发表时间：
2014-07-03
期刊：
影响因子：
64.5
通讯作者：
Hahn WC
中科院分区：
文献类型：
--
作者：
Shao DD;Xue W;Krall EB;Bhutkar A;Piccioni F;Wang X;Schinzel AC;Sood S;Rosenbluh J;Kim JW;Zwang Y;Roberts TM;Root DE;Jacks T;Hahn WC
Cancer cells that express oncogenic alleles of RAS typically require sustained expression of the mutant allele for survival, but the molecular basis of this oncogene dependency remains incompletely understood. To identify genes that can functionally substitute for oncogenic RAS, we systematically expressed 15,294 open reading frames in a human KRAS-dependent colon cancer cell line engineered to express an inducible KRAS-specific shRNA. We found 147 genes that promoted survival upon KRAS suppression. In particular, the transcriptional co-activator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation. Acquired resistance to Kras suppression in a Kras-driven murine lung cancer model also involved increased YAP1 signaling. KRAS and YAP1 converge on the transcription factor FOS and activate a transcriptional program involved in regulating the epithelial-mesenchymal transition (EMT). Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling.
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影响因子：
64.5
作者：
Kapoor A;Yao W;Ying H;Hua S;Liewen A;Wang Q;Zhong Y;Wu CJ;Sadanandam A;Hu B;Chang Q;Chu GC;Al-Khalil R;Jiang S;Xia H;Fletcher-Sananikone E;Lim C;Horwitz GI;Viale A;Pettazzoni P;Sanchez N;Wang H;Protopopov A;Zhang J;Heffernan T;Johnson RL;Chin L;Wang YA;Draetta G;DePinho RA
通讯作者：
DePinho RA
影响因子：
3.9
作者：
O'Donnell, Amanda;Odrowaz, Zaneta;Sharrocks, Andrew D.
通讯作者：
Sharrocks, Andrew D.
影响因子：
3.8
作者：
Lau, Ken S.;Haigis, Kevin M.
通讯作者：
Haigis, Kevin M.
影响因子：
50.3
作者：
Lim, KH;Counter, CM
通讯作者：
Counter, CM
影响因子：
5.3
作者：
LEDWITH, BJ;MANAM, S;BRADLEY, MO
通讯作者：
BRADLEY, MO