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USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT
- Source :
- Cancer Cell International, Vol 24, Iss 1, Pp 1-14 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Ubiquitination was considered to be a crucial factor in intrahepatic cholangiocarcinoma (iCCA) development. Herein, we identified Ubiquitin-specific peptidase 8 (USP8) as a key regulator for promoting the tumorigenesis of iCCA cell via stabilizing OGT. USP8 was overexpressed in human tumor tissues and correlated with worse survival. Moreover, the mass spectrometry and co-immunoprecipitation analysis indicated that USP8 interacted with OGT. USP8 worked as a bona fide deubiquitylase of OGT. It stabilized OGT in a deubiquitylation activity-dependent manner. Meanwhile, DUB-IN3, the USP8 inhibitor, could also restrain the malignancy of intrahepatic cholangiocarcinoma. In addition, USP8 depletion promoted the response of iCCA to pemigatinib. In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating enzyme of OGT. The USP8-OGT axis could be a potential target for iCCA therapy.
Details
- Language :
- English
- ISSN :
- 14752867
- Volume :
- 24
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cancer Cell International
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2d3f94fe66ee4f52a901a72b8fe3f45e
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12935-024-03370-w