Cooperation between Notch and CXCR4/SDF1a axis in ovarian cancer

Ovarian cancer (OC) is the most aggressive gynaecological cancer. Understanding OC molecular pathogenesis is critical to provide novel therapeutic strategies. We aim to elucidate Notch oncogenic role in OC by focusing on its extensive crosstalk with other important pathways as CXCR4/SDF1 chemokine system whose involvement in OC development and metastasis is well recognized. The analyzed OC cell lines high levels of CXCR4 and its ligand SDF1. Treatment with DAPT, an inhibitor of Notch activity, reduced OC cell proliferation and blocked cell cycle in G0/G1 phase without affecting apoptosis. In addition, Notch withdrawal diminished CXCR4 and SDF1 expression levels and hampered SDF1-driven migration and proliferation. In conclusion, Notch deregulation might affect important features of OC such as cell growth and migration through the modulation of CXCR4/SDF1a pathway. This indicates that these intertwined pathways are promising therapeutic targets in OC.