title: DEDD, a novel tumor repressor, reverses epithelial-mesenchymal transition by activating selective autophagy.
abstract: Metastasis is the spread of cancer cells from their primary location to other parts of the body. Metastatic cancer is responsible for most cancer deaths. Increasing evidence indicates that epithelial-mesenchymal transition (EMT), a crucial developmental program, contributes to control cancer invasion and metastasis. We recently reported that death effector domain-containing DNA-binding protein (DEDD), a key effector molecule for cell death signaling receptors, attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that DEDD physically interacts with the class III PtdIns 3-kinase complex containing PIK3C3 and BECN1, which controls critical aspects of autophagy; this interaction activates autophagy and induces the autophagy-mediated lysosomal degradation of SNAI/Snail and TWIST, two master inducers of the EMT process. Further study reveals that the DEDD-PIK3C3 interaction can support the stability of PIK3C3 to maintain autophagic activity and promote the degradation of SNAI and TWIST. Our finding indicates that DEDD is a prognostic marker and a potential therapeutic target for the prevention and treatment of cancer metastasis. Moreover, regulation of the DEDD-PIK3C3 interaction may serve as an entry point to translate modifiers of this interaction into clinical endpoints.
authors.affiliation: Molecular Immunology and Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Zhuo-Wei
authors.initials: ZW
authors.lastname: Hu
mesh_terms: D001343:Autophagy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D059748:Proteolysis; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins