Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 25, Pages 9241-9246Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1322913111
Keywords
SQSTM1; melanoma; skin cancer; ubiquitination; proteasome
Categories
Funding
- National Institutes of Health (NIH)/National Institute on Environmental Health Sciences [ES016936]
- American Cancer Society [RSG-13-078-01]
- University of Chicago Cancer Research Center [P30 CA014599]
- CTSA [NIH UL1RR024999]
- University of Chicago Friends of Dermatology Endowment Fund
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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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