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Downregulation of CHIP promotes ovarian cancer metastasis by inducing Snail-mediated epithelial-mesenchymal transition

 Sun‐Mi Park  ;  Seung‐Ho Park  ;  Ki‐Jun Ryu  ;  In‐Kyu Kim  ;  Hyeontak Han  ;  Hyo‐Jin Kim  ;  Seon‐Hee Kim  ;  Keun‐Seok Hong  ;  Hyemin Kim  ;  Minju Kim  ;  Bok Im Cho  ;  Jeong Doo Heo  ;  Na Hyun Kim  ;  Eun Mi Hwang  ;  Jae‐Yong Park  ;  Jong In Yook  ;  Hee Jun Cho  ;  Cheol Hwangbo  ;  Kwang Dong Kim  ;  Hoseok Song  ;  Jiyun Yoo 
 Molecular Oncology, Vol.13(5) : 1280-1295, 2019 
Journal Title
 Molecular Oncology 
Issue Date
CHIP ; E3 ubiquitin ligase ; EMT ; cancer metastasis ; ovarian cancer ; snail
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
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