RETRACTED: Regulation of cell proliferation and migration by p62 through stabilization of Twist1 (Retracted article. See vol. 120, 2023)

被引:191
|
作者
Qiang, Lei [1 ]
Zhao, Baozhong [1 ]
Ming, Mei [1 ]
Wang, Ning [2 ]
He, Tong-Chuan [2 ]
Hwang, Seungmin [3 ]
Thorburn, Andrew [4 ,5 ]
He, Ying [1 ]
机构
[1] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA
[3] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[4] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA
[5] Hlth Sci Ctr, Aurora, CO 80045 USA
基金
美国国家卫生研究院;
关键词
SQSTM1; melanoma; skin cancer; ubiquitination; proteasome; EPITHELIAL-MESENCHYMAL TRANSITION; CADHERIN GENE-EXPRESSION; AUTOPHAGY; DEGRADATION; ACTIVATION; SNAIL; P62/SQSTM1; PROTEASOME; PROMOTES; NRF2;
D O I
10.1073/pnas.1322913111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The selective autophagy substrate p62 serves as a molecular link between autophagy and cancer. Suppression of autophagy causes p62 accumulation and thereby contributes to tumorigenesis. Here we demonstrate that autophagy deficiency promotes cell proliferation and migration through p62-dependent stabilization of the oncogenic transcription factor Twist1. p62 binds to Twist1 and inhibits degradation of Twist1. In mice, p62 up-regulation promotes tumor cell growth and metastasis in a Twist1-dependent manner. Our findings demonstrate that Twist1 is a key downstream effector of p62 in regulation of cell proliferation and migration and suggest that targeting p62-mediated Twist1 stabilization is a promising therapeutic strategy for prevention and treatment of cancer.
引用
收藏
页码:9241 / 9246
页数:6
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