Xie Mian, Wu Xiaojun, Zhang Jinjun, Zhang Jiexia, Li Xiangxiang
China State Key Laboratory of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Oncology in Southern China, Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
Mol Carcinog. 2017 Oct;56(10):2178-2189. doi: 10.1002/mc.22661. Epub 2017 Jul 28.
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro- and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15 ) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway. Ski inhibited TAZ by increasing their phosphorylation by Lats2 and did not alter the localization of TAZ. Ski inhibited lung cancer growth and invasion. Ski methylation correlated with decreased mRNA expression in human lung cancer cell lines. Thus, Ski inhibited the function of TGF-β and TAZ through multiple mechanisms in human lung cancer.
Ski是禽斯隆-凯特琳逆转录病毒的转化蛋白，在人类癌症中既表现出促癌活性又表现出抑癌活性。这些相互矛盾的观察结果背后的机制尚未完全了解。在此，我们研究了Ski抑癌活性的潜在机制。为了研究Ski重新激活对TGF-β和Hippo/TAZ信号通路的影响，我们测量了其对内源性Smad靶基因（PAI-1和P15）和TAZ靶基因CTGF的影响。结果表明，Ski在TGF-β1/Smad信号通路中发挥其抑制活性。Ski通过增加Lats2对TAZ的磷酸化来抑制TAZ，并且不改变TAZ的定位。Ski抑制肺癌的生长和侵袭。Ski甲基化与人类肺癌细胞系中mRNA表达降低相关。因此，Ski在人类肺癌中通过多种机制抑制TGF-β和TAZ的功能。
