Autophagy deficiency stabilizes TWIST1 to promote epithelial-mesenchymal transition

被引：75

作者：

Qiang, Lei ^{[1
]}

He, Yu-Ying ^{[1
]}

机构：

[1] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA

来源：

AUTOPHAGY | 2014年 / 10卷 / 10期

关键词：

autophagosome; autophagy; EMT; melanoma; metastasis; p62; proteasome; skin cancer; tumor growth; TWIST1;

D O I：

10.4161/auto.32171

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The transcription factor TWIST1 is a basic helix-loop-helix protein that regulates epithelial-mesenchymal transition (EMT) in early embryonic morphogenesis, cancer development, and cancer metastasis. The regulation of TWIST1 remains poorly understood. Recently, we found that autophagy deficiency stabilizes TWIST1 protein through SQSTM1/p62 accumulation. SQSTM1 binds with TWIST1 to inhibit TWIST1 degradation in both autophagosomes and proteasomes. SQSTM1-mediated TWIST1 stabilization promotes EMT in vitro, and tumor growth and metastasis in mice. We propose autophagy as a new mechanism to control the TWIST1 protein levels and activity in cancer development and progression.

引用

页码：1864 / 1865

页数：2