USP7 inhibition perturbs proteostasis and tumorigenesis in triple-negative breast cancer.

ABSTRACT: The deubiquitinase USP7 is a critical regulator of tumorigenesis, known for stabilizing the MDM2-p53 pathway. Emerging evidence highlights USP7's p53-independent roles in proliferation and tumorigenesis. Our study reveals that USP7 is broadly upregulated in breast cancer, including triple-negative breast cancer (TNBC), a subtype characterized by near-universal TP53 loss. This provides a model to investigate p53-independent functions of USP7. Using TNBC models, we define p53-independent roles of USP7 in regulating proteostasis and tumorigenesis. Importantly, genetic and pharmacologic USP7 inactivation impaired tumor progression in TNBC models. To explore USP7's role in p53-mutant TNBCs, we performed deep quantitative proteomics across TNBC cell lines, identifying shared USP7 targets involve

SUBMITTER: Kim A 

PROVIDER: S-EPMC13473141 | biostudies-literature | 2026 May

REPOSITORIES: biostudies-literature