The deubiquitinating enzyme USP1 modulates ER? and modulates breast cancer progression.

ABSTRACT: Breast cancer is one of the most common malignancies worldwide, while the luminal types (ER? positive) accounts for two third of all breast cancer cases. Although ER? positive breast cancer could be effective controlled by endocrine therapy, most of the patients will develop endocrine resistance, which becomes a headache clinical issue for breast cancer field. Endocrine resistance could be caused by multiple pathway disorders, the dys-regulation of ER? signaling might be a critical factor, which makes it urgent and important to reveal the potential molecular mechanism of ER? signaling. In our current study, we identified a new deubiquitination enzyme USP1 through screening the whole DUB (Deubiquitinases) siRNA library. The expression of USP1 is elevated in human breast cancer compared with normal mammary tissues. Importantly, USP1 expression levels are specially correlated with poor survival in ER? positive patients. USP1 depletion inhibited breast cancer cell progression and ER? signaling activity. Immuno-precipitation assays indicate that USP1 associates with ER? and promotes its stability possibly via inhibiting ER? K48-linked poly-ubiquitination. In conclusion, our data implicate a non-genomic mechanism by USP1 via stabilizing ER? protein controls ER? target gene expression linked to breast cancer progression.

SUBMITTER: Niu Z 

PROVIDER: S-EPMC7591989 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature