Global Proteomic Analysis of Ovarian Clear Cell Carcinoma Cells Lacking ARID1A Reveals Upregulated Mitochondrial Electron Transport Chain Activity

Ovarian clear cell carcinoma (OCCC) is the most lethal gynecological cancer. It is characterized by somatic inactivating mutations of ARID1A, a component of the SWI/SNF chromatin-remodeling complex, occurring in up to 70% of patients. Patients with these mutations in their tumors have considerably poorer outcomes compared to those without such mutations. ARID1A-deficient cells have been shown to have a higher dependence on mitochondrial respiration, suggesting that targeting mitochondrial respiration is a promising approach to eliminating ARID1A-deficient cancer cells. Here we generated and characterized OCCC-derived ARID1A wild type and knock-out cell lines. Our proteomic data provide evidence of the increased relative abundance of mETC proteins in the ARID1A knock-out OCCC cells. Taken together, our data provides a rationale for identifying therapeutic vulnerabilities within the mETC in the context of treating ARID1A-deficient OCCC.