RETRACTED: Regulation of cell proliferation and migration by p62 through stabilization of Twist1

• DOI: 10.1073/pnas.1322913111
• Publication Date: 2014-06-10T07:46:19Z
• Authors: Lei Qiang; Baozhong Zhao; Mei Ming; Ning Wang; Tong-Chuan He; Seungmin Hwang; Andrew Thorburn; Yu-Ying He
• Keywords: Male; Mice, Knockout; 0303 health sciences; Protein Stability; Twist-Related Protein 1; Nuclear Proteins; Neoplasm Proteins; 3. Good health; Mice; 03 medical and health sciences; HEK293 Cells; Cell Movement; Neoplasms; Sequestosome-1 Protein; Animals; Humans; Female; Neoplasm Metastasis; Heat-Shock Proteins; Adaptor Proteins, Signal Transducing; Cell Proliferation; HeLa Cells

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.