Park, Sun-Mi Park, Seung-Ho Ryu, Ki-Jun Kim, In-Kyu Han, Hyeontak Kim, Hyo-Jin Kim, Seon-Hee Hong, Keun-Seok Kim, Hyemin Kim, Minju Cho, Bok Im Heo, Jeong Doo Kim, Na Hyun Hwang, Eun Mi Park, Jae-Yong Yook, Jong In Cho, Hee Jun Hwangbo, Cheol Kim, Kwang Dong Song, Hoseok Yoo, Jiyun 2024-01-19T20:03:51Z 2024-01-19T20:03:51Z 2021-09-02 2019-05 1574-7891 https://pubs.kist.re.kr/handle/201004/120056 The epithelial-mesenchymal transition (EMT) plays a pivotal role in the conversion of early-stage tumors into invasive malignancies. The transcription factor Snail, an extremely unstable protein whose subcellular levels are regulated by many E3 ubiquitin ligases, promotes EMT as well as associated pathological characteristics including migration, invasion, and metastasis. Through yeast two-hybrid screening, we identified the carboxyl terminus of Hsc70-interacting protein (CHIP) as a novel Snail ubiquitin ligase that interacts with Snail to induce ubiquitin-mediated proteasomal degradation. Inhibition of CHIP expression increases Snail protein levels, induces EMT, and enhances in vitro migration and invasion as well as in vivo metastasis of ovarian cancer cells. In turn, Snail depletion abrogates all phenomena induced by CHIP depletion. Finally, Snail and CHIP expression is inversely correlated in ovarian tumor tissues. These findings establish the CHIP-Snail axis as a post-translational mechanism of EMT and cancer metastasis regulation. English WILEY TUMOR-METASTASIS GENE-EXPRESSION PHOSPHORYLATION DEGRADATION SUPPRESSOR STABILIZATION PROTEIN Downregulation of CHIP promotes ovarian cancer metastasis by inducing Snail-mediated epithelial-mesenchymal transition Article 10.1002/1878-0261.12485 1 MOLECULAR ONCOLOGY, v.13, no.5, pp.1280 - 1295 MOLECULAR ONCOLOGY 13 5 1280 1295 scie scopus 000477090700021 2-s2.0-85065021617 Oncology Oncology Article TUMOR-METASTASIS GENE-EXPRESSION PHOSPHORYLATION DEGRADATION SUPPRESSOR STABILIZATION PROTEIN cancer metastasis CHIP E3 ubiquitin ligase EMT ovarian cancer snail