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

Molecular Oncology

Eun Mi Hwang¹  Hoseok Song²  Jong In Yook³  Kwang Dong Kim⁴  Hyemin Kim⁴  Keun‐Seok Hong⁴  Ki‐Jun Ryu⁴  Sun‐Mi Park⁴  Minju Kim⁴  Seon‐Hee Kim⁴  Hyo‐Jin Kim⁴  Jiyun Yoo⁴  Cheol Hwangbo⁴  Hyeontak Han⁴  In‐Kyu Kim⁴  Seung‐Ho Park⁵  Bok Im Cho⁶  Jeong Doo Heo⁶  Na Hyun Kim⁶  Hee Jun Cho⁷  Jae‐Yong Park⁸ 

[1] Center for Functional Connectomics Korea Institute of Science and Technology Seoul Korea;Department of Biomedical Sciences College of Medicine Korea University Seoul Korea;Department of Oral Pathology Oral Cancer Research Institute College of Dentistry Yonsei University Seoul Korea;Division of Applied Life Science (BK21 Plus) Research Institute of Life Sciences Gyeongsang National University Jinju Korea;Environmental Disease Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea;Gyeongnam Department of Environmental Toxicology and Chemistry Toxicology Screening Center Korea Institute of Toxicology Jinju Korea;Immunotherapy Convergence Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea;School of Biosystem and Biomedical Science College of Health Science Korea University Seoul Korea;

关键词: cancer metastasis;    CHIP;    E3 ubiquitin ligase;    EMT;    ovarian cancer;    snail;   

DOI  :  10.1002/1878-0261.12485

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown