Regulation of Cell Proliferation and Migration by P62 Through Stabilization of Twist1

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2014 Jun 14

PMID 24927592

Citations 137

Authors

Lei Qiang

Baozhong Zhao

Mei Ming

Ning Wang

Tong-Chuan He

Seungmin Hwang

Andrew Thorburn

Yu-Ying He

Affiliations

Soon will be listed here.

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.

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