DNAJB9 suppresses the metastasis of triple-negative breast cancer by promoting FBXO45-mediated degradation of ZEB1
- Authors
- Kim, Hye-Youn; Kim, Young-Mi; Hong, Suntaek
- Issue Date
- 8-May-2021
- Publisher
- SPRINGERNATURE
- Citation
- CELL DEATH & DISEASE, v.12, no.5
- Journal Title
- CELL DEATH & DISEASE
- Volume
- 12
- Number
- 5
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/81200
- DOI
- 10.1038/s41419-021-03757-x
- ISSN
- 2041-4889
- Abstract
- DNAJB9, a member of the heat shock protein 40 family, acts as a multifunctional player involved in the maintenance of their client proteins and cellular homeostasis. However, the mechanistic action of DNAJB9 in human malignancies is yet to be fully understood. In this study, we found that ectopic restoration of DNAJB9 inhibits the migration, invasion, in vivo metastasis, and lung colonization of triple-negative breast cancer (TNBC) cells. Mechanistically, DNAJB9 stabilizes FBXO45 protein by suppressing self-ubiquitination and reduces the abundance of ZEB1 by Lys48-linked polyubiquitination to inhibit the epithelial–mesenchymal transition (EMT) and metastasis. Clinically, the reduction of DNAJB9 expression, concomitant with decreased FBXO45 abundance in breast cancer tissues, correlates with poorer clinical outcomes of patients with breast cancer. Taken together, our results provide a novel insight into the metastasis of TNBC and define a promising therapeutic strategy for cancers with overactive ZEB1 by regulating the DNAJB9–FBXO45 signaling axis. © 2021, The Author(s).
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의예과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/81200)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.