Kao S.-H.Wang W.-L.Chen C.-Y.YIH-LEONG CHANGWu Y.-Y.Wang Y.-T.Wang S.-P.Nesvizhskii A.I.Chen Y.-J.Hong T.-M.PAN-CHYR YANG2020-12-022020-12-0220140950-9232https://www.scopus.com/inward/record.uri?eid=2-s2.0-84902528711&doi=10.1038%2fonc.2013.279&partnerID=40&md5=9c20f0ba33ffb7c581df6bec8f2f77b0https://scholars.lib.ntu.edu.tw/handle/123456789/523529Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer. ? 2014 Macmillan Publishers Limited All rights reserved.[SDGs]SDG3carboxyl terminus of heat shock cognate protein 70 interacting protein; glycogen synthase kinase 3beta; protein; transcription factor Slug; unclassified drug; article; cancer cell; cell invasion; cell migration; controlled study; epithelial mesenchymal transition; lung non small cell cancer; metastasis; nucleotide sequence; priority journal; protein degradation; protein expression; protein phosphorylation; protein protein interaction; ubiquitination; Animals; Blotting, Western; Cadherins; Carcinoma, Non-Small-Cell Lung; Cell Movement; Cell Proliferation; Cohort Studies; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3; Humans; Immunoenzyme Techniques; Immunoprecipitation; Lung Neoplasms; Mice; Mice, Inbred NOD; Mice, Nude; Phosphorylation; Proteolysis; Proteomics; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription Factors; Tumor Cells, Cultured; Ubiquitin; Ubiquitin-Protein Ligases; Xenograft Model Antitumor Assaysjournal article10.1038/onc.2013.279238514952-s2.0-84902528711