Proteomic profiling of CYP11A1 overexpressed kidney cancer cell lines

Abstract

Our study focused on the comparison between proteomic profiling of CYP11A1 overexpressed normal and cancer kidney cell lines. According to the International Agency for Research on Cancer, kidney cancer is the 12th cause of death from cancer worldwide which is currently showed a poor prognosis [1]. CYP11A1 is a mitochondrial side-chain cleavage enzyme catalyze the initial step in the conversion of cholesterol to pregnenolone. The expression of CYP11A1 was rapidly downregulated in six cancer types including colon adenocarcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, lung squamous cell carcinoma, prostate adenocarcinoma and uterine corpus endometrial carcinoma [2]. Our study indicated overexpression of CYP11A1 can inhibited cancer cells migration and invasion. To explain how CYP11A1 can inhibit cell migration and invasion, we compared proteomic profiling of CYP11A1-transfection and non-transfection in cancer cell lines. A total of 218 and 161 proteins were identified with high confidence (Score Sequest HT >1, p-value<0.05 and Exp. q-value<0.005) entries in A498 and Caki-1 respectively. Among these proteins, 78 proteins were overlapped between CYP11A1-overexpressed and non-transfected kidney cancer cell lines. Ingenuity Pathway Analysis (IPA) showed enrichment of many cancer-related biological processes and pathways such as EIF2, mTOR, EIF4 and p70S6K signaling. These results hypothesized that activating steroid biosynthesis may be useful to block cancer progression and targeting of CYP11A1 catalyzes the first step of steroidogenesis as a potential therapeutic target for kidney cancer.