内皮素通过激活YAP/TAZ促进结直肠癌发生。
Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ.
作者信息
Wang Zhen, Liu Peng, Zhou Xin, Wang Tianxiang, Feng Xu, Sun Yi-Ping, Xiong Yue, Yuan Hai-Xin, Guan Kun-Liang
机构信息
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.
出版信息
Cancer Res. 2017 May 1;77(9):2413-2423. doi: 10.1158/0008-5472.CAN-16-3229. Epub 2017 Mar 1.
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. .
摘要
内皮素受体A（ETAR）通过刺激细胞增殖、迁移和存活来促进肿瘤发生。然而，ETAR促进肿瘤生长的机制在很大程度上尚不清楚。在本研究中，我们证明ETAR通过激活YAP/TAZ（Hippo肿瘤抑制途径的两个转录共激活因子）来刺激结肠细胞增殖、迁移和肿瘤发生。内皮素-1处理诱导多种结肠癌细胞中YAP/TAZ去磷酸化、核积累和转录激活。ETAR刺激通过下游G蛋白Gαq/11和Rho GTPase发挥作用，以抑制Hippo途径，从而导致YAP/TAZ激活，这是ETAR诱导肿瘤发生所必需的。总体而言，这些结果表明YAP/TAZ轴在ETAR信号传导中起关键作用。
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