作者
Ming-Yang Li, Lin-Ni Fan, Dong-Hui Han, Zhou Yu, Jing Ma, Yi-Xiong Liu, Pei-Feng Li, Dan-Hui Zhao, Jia Chai, Lei Jiang, Shi-Liang Li, Juan-Juan Xiao, Qiu-Hong Duan, Jing Ye, Mei Shi, Yong-Zhan Nie, Kai-Chun Wu, Dezhong Joshua Liao, Yu Shi, Yan Wang, Qing-Guo Yan, Shuang-Ping Guo, Xiu-Wu Bian, Feng Zhu, Jian Zhang, Zhe Wang
发表日期
2020/8/3
期刊
The Journal of clinical investigation
卷号
130
期号
8
页码范围
4301-4319
出版商
American Society for Clinical Investigation
简介
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of ΔNp63α, the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the β-catenin signaling pathway through direct phosphorylation of GSK-3β at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties …
学术搜索中的文章
MY Li, LN Fan, DH Han, Z Yu, J Ma, YX Liu, PF Li… - The Journal of clinical investigation, 2020