title: 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.affiliation: Section of Dermatology; Department of Medicine; University of Chicago; Chicago, IL USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiang
authors.affiliation: Section of Dermatology; Department of Medicine; University of Chicago; Chicago, IL USA.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: He
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051879:Twist-Related Protein 1; D046988:Proteasome Endopeptidase Complex
keywords: EMT; TWIST1; autophagosome; autophagy; melanoma; metastasis; p62; proteasome; skin cancer; tumor growth