USP1 and SNAI1 identified as targets in ovarian cancer

INDICATION: Ovarian cancer

Patient sample, cell culture and mouse studies suggest inhibiting USP1 or its deubiquitination target SNAI1 could help treat ovarian cancer. In patients, high tumor levels of USP1 mRNA were associated with poor progression-free and overall survival. In three human ovarian cancer cell lines, a tool compound USP1 inhibitor or the USP1 inhibitor pimozide increased sensitivity to cisplatin compared with no treatment. In one of the cell lines, knockout of USP1 or two shRNAs targeting SNAI1 increased sensitivity to cisplatin compared with normal USP1 expression or a non-targeting shRNA, respectively. In a cell-based invasion assay, USP1 knockout or an shRNA targeting USP1 decreased invasiveness. In a xenograft mouse model of metastatic ovarian cancer, tumor-specific USP1 knockout decreased tumor growth compared with normal USP1 expression. Ongoing work includes studying the molecular mechanisms linking USP1 to cancer cell dissemination and DNA repair following chemotherapy...