Regulation of cell proliferation and migration by p62 through stabilization of Twist1.
Proc Natl Acad Sci U S A
; 111(25): 9241-6, 2014 Jun 24.
Article
em En
| MEDLINE
| ID: mdl-24927592
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Proteínas Adaptadoras de Transdução de Sinal
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Proteína 1 Relacionada a Twist
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Proteínas de Choque Térmico
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Proteínas de Neoplasias
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Neoplasias
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article