Regulation of cell proliferation and migration by p62 through stabilization of Twist1.

Qiang, Lei, Baozhong Zhao, Mei Ming, Ning Wang, Tong-Chuan He, Seungmin Hwang, Andrew Thorburn, and Yu-Ying He. 2014. “Regulation of Cell Proliferation and Migration by P62 through Stabilization of Twist1.”. Proceedings of the National Academy of Sciences of the United States of America 111 (25): 9241-6.

Abstract

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.

Last updated on 01/02/2024
PubMed