The Deubiquitinating Enzyme Usp1 Modulates Er Alpha And Modulates Breast Cancer Progression

Breast cancer is one of the most common malignancies worldwide, while the luminal types (ER alpha positive) accounts for two third of all breast cancer cases. Although ER alpha 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 alpha signaling might be a critical factor, which makes it urgent and important to reveal the potential molecular mechanism of ER alpha 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 alpha positive patients. USP1 depletion inhibited breast cancer cell progression and ER alpha signaling activity. Immuno-precipitation assays indicate that USP1 associates with ER alpha and promotes its stability possibly via inhibiting ER alpha K48-linked poly-ubiquitination. In conclusion, our data implicate a non-genomic mechanism by USP1 via stabilizing ER alpha protein controls ER alpha target gene expression linked to breast cancer progression.