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The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness.

Authors :
Li, Fengtian
Hu, Qingyong
He, Tao
Xu, Jing
Yi, Yong
Xie, Siyi
Ding, Liangping
Fu, Mengyuan
Guo, Rongtian
Xiao, Zhi-Xiong Jim
Niu, Mengmeng
Source :
Cancers; Jun2020, Vol. 12 Issue 6, p1582, 1p
Publication Year :
2020

Abstract

Lung cancer stem cells (CSCs) play a pivotal role in tumor development, drug resistance, metastasis and recurrence of lung cancer. Thus, it is of great importance to study the mechanism by which CSCs are regulated. In this study, we demonstrate that the deubiquitinase USP4 is critically important in promoting lung cancer stemness. Silencing of USP4 leads to reduction of Oct4 and Sox2 expression, decreased CD133+ cell population and inhibition of tumorsphere formation. Conversely, ectopic expression of USP4 significantly enhances lung cancer cell stemness, which is effectively rescued by simultaneous silencing of Twist1. Mechanistically, we identified USP4 as a novel deubiquitinase of Twist1. USP4 binds to, deubiquitinates and stabilizes Twist1 protein. Furthermore, we show that USP4 expression is elevated in human lung cancer specimens and is positively correlated with Twist1 expression. High expression of USP4/Twist1 is associated with poor clinical outcomes of lung cancer patients. Together, this study highlights an important role for USP4 in lung cancer stemness and suggests USP4 as a potential target for lung cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726694
Volume :
12
Issue :
6
Database :
Complementary Index
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
144495824
Full Text :
https://doi.org/10.3390/cancers12061582