title: Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ.
abstract: Endothelin receptor A (ETAR) promotes tumorigenesis by stimulating cell proliferation, migration, and survival. However, the mechanism of ETAR in promoting tumor growth is largely unknown. In this study, we demonstrate that ETAR stimulates colon cell proliferation, migration, and tumorigenesis through the activation of YAP/TAZ, two transcription coactivators of the Hippo tumor suppressor pathway. Endothelin-1 treatment induced YAP/TAZ dephosphorylation, nuclear accumulation, and transcriptional activation in multiple colon cancer cells. ETAR stimulation acted via downstream G-protein Gαq/11 and Rho GTPase to suppress the Hippo pathway, thus leading to YAP/TAZ activation, which was required for ETAR-induced tumorigenesis. Overall, these results indicate a critical role of the YAP/TAZ axis in ETAR signaling.Cancer Res; 77(9); 2413-23. ©2017 AACR.
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Sun
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. kuguan@ucsd.edu yxiong@unc.edu yuanhaixin@fudan.edu.cn.|Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. kuguan@ucsd.edu yxiong@unc.edu yuanhaixin@fudan.edu.cn.
authors.forename: Hai-Xin
authors.initials: HX
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. kuguan@ucsd.edu yxiong@unc.edu yuanhaixin@fudan.edu.cn.|Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California.
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D019332:Endothelin-1 / Q000008:administration & dosage / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D044022:Receptor, Endothelin A / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000091102:YAP-Signaling Proteins; D020741:rho GTP-Binding Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019332:Endothelin-1; D044385:GTP-Binding Protein alpha Subunits; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D044022:Receptor, Endothelin A; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D020741:rho GTP-Binding Proteins