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

Title
Downregulation of CHIP promotes ovarian cancer metastasis by inducing Snail-mediated epithelialmesenchymal transition
Authors
황은미Sun-Mi ParkSeung-Ho ParkKi-Jun RyuIn-Kyu KimHyeontak HanHyo-Jin KimSeon-Hee KimKeun-Seok HongHyemin KimMinju KimBok Im ChoJeong Doo HeoNa Hyun KimJae-Yong ParkJong In YookHee Jun ChoCheol HwangboKwang Dong KimHoseok SongJiyun Yoo
Issue Date
2019-05
Publisher
MOLECULAR ONCOLOGY
Citation
VOL 13, NO 5-1295
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/69264
ISSN
1574-7891
Appears in Collections:
KIST Publication > Article
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