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Endothelin promotes colorectal tumorigenesis by activating YAP/TAZ

Cancer Research,. 2018; 
Zhen Wang , , Peng Liu, , Xin Zhou, , Tianxiang Wang, , Xu Feng, , Yi-Ping Sun , Yue Xiong, , Hai-Xin Yuan and Kun-Liang Guan,
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Mouse TNFα was purchased from Genscript (Z02918) and administered to the resistant Ccm2ECKO neonatal CCM disease model under identical conditions as the IL-1β experiments.

摘要

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 co-activators of the Hippo tumor suppressor pathway. Endothelin-1 (ET-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-indu... More

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