Autophagy deficiency stabilizes TWIST1 to promote epithelial-mesenchymal transition.

Abstract

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.

• Authors: Lei Qiang, Yu-Ying He
• Journal: Autophagy (Autophagy) Vol. 10 Issue 10 Pg. 1864-5 (Oct 01 2014) ISSN: 1554-8635 [Electronic] United States
• PMID: 25126736 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Twist-Related Protein 1
• Proteasome Endopeptidase Complex

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Autophagy
• Epithelial-Mesenchymal Transition
• Humans
• Lysosomes (metabolism)
• Mice
• Models, Biological
• Proteasome Endopeptidase Complex (metabolism)
• Protein Stability
• Twist-Related Protein 1 (metabolism)