Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolism proteins

Epithelial Ovarian Cancer (EOC) is associated with dismal survival rates due to the fact that patients are frequently diagnosed at an advanced stage and eventually become resistant to traditional chemotherapeutics. Hence, there is a crucial need for new and innovative therapies. Septin-2, a member of the septin family of GTP binding proteins, has been characterized in EOC for the first time and represents a potential future target. Septin-2 was found to be overexpressed in serous and clear cell human patient tissue compared to benign disease. Stable septin-2 knockout clones developed in an ovarian cancer cell line exhibited a significant decrease in proliferation rates. Comparative label-free proteomic analysis of septin-2 knockout cells revealed differential protein expression of pathways associated with the TCA cycle, acetyl CoA, proteasome and spliceosome,. Further validation of target proteins indicate that septin-2 plays a predominant role in post-transcriptional and translational modifications as well as cellular metabolism, and are the first to suggest the potential novel role of septin-2 in promoting EOC tumorigenesis through these mechanisms.