TY - JOUR
T1 - Endothelin promotes colorectal tumorigenesis by activating YAP/TAZ
AU - Wang, Zhen
AU - Liu, Peng
AU - Zhou, Xin
AU - Wang, Tianxiang
AU - Feng, Xu
AU - Sun, Yi Ping
AU - Xiong, Yue
AU - Yuan, Hai Xin
AU - Guan, Kun Liang
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85019042219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019042219&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-16-3229
DO - 10.1158/0008-5472.CAN-16-3229
M3 - Article
C2 - 28249901
AN - SCOPUS:85019042219
SN - 0008-5472
VL - 77
SP - 2413
EP - 2423
JO - Cancer Research
JF - Cancer Research
IS - 9
ER -