Notch regulates the growth-promoting nitric oxide cGMP-dependent pathway in epithelial ovarian cancer and ovarian surface epithelium cells

Abstract

Ovarian cancer is the leading cause of mortality among gynecologic cancers. There are several subtypes of ovarian cancer, amongst which epithelial ovarian cancer (EOC) makes up to 90% of all ovarian cancers. The current treatment for EOC consists of debulking surgery followed by a chemotherapeutic regimen composed of platinum-derivative/paclitaxel agents. This regimen is inefficient due to the high rate of chemoresistance development. Thus, targeted therapeutic strategies are in demand in order to control this disease. To this end, a better understanding of the molecular pathways and mechanisms underlying the initiation and development of EOC is required. Here, we report the interaction between the oncogenic Notch and nitric oxide (NO) pathways and provide novel insights into the molecular nature of this interaction. Moreover, we show that NO signaling promotes the growth of EOC cells in vitro and propose blocking this pathway as a potential targeted therapeutic strategy in EOC.