USP10-mediated deubiquitination and activation of <i>KRAS</i> mutants promotes colorectal cancer <i>via</i> a novel USP10/KRAS positive feedback circuit.

ABSTRACT: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is associated with the poor prognosis of colorectal cancer (CRC) patients, but the therapeutic strategies targeting KRAS are limited, and novel intervention strategies are urgently needed. The dysfunction of deubiquitinases (DUBs) is widely involved in the progression of malignancy, and DUBs are considered ideal anti-tumor targets due to their well-defined structures and catalytic sites. In our study, through DUB inhibitors screening and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identified that ubiquitin-specific protease 10 (USP10) functions as a potent DUB regulating KRAS mutants' activity. Mechanistically, USP10 directly binds to and promotes KRAS variants' activity across different mut

SUBMITTER: Yuan T 

PROVIDER: S-EPMC12827889 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature