title: Regulation of cell proliferation and migration by p62 through stabilization of Twist1.
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.
authors.affiliation: Departments of Medicine, Section of Dermatology.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiang
authors.affiliation: Departments of Medicine, Section of Dermatology.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Departments of Medicine, Section of Dermatology.
authors.forename: Mei
authors.initials: M
authors.lastname: Ming
authors.affiliation: Orthopaedic Surgery and Rehabilitation Medicine, and.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Orthopaedic Surgery and Rehabilitation Medicine, and.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Pathology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Seungmin
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thorburn
authors.affiliation: Departments of Medicine, Section of Dermatology, yyhe@medicine.bsd.uchicago.edu.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: He
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D000071456:Sequestosome-1 Protein; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse
keywords: SQSTM1; melanoma; proteasome; skin cancer; ubiquitination