Ovarian Cancer (OC) cells initially spread throughout the peritoneal cavity via extension or by detaching often in clusters from primary tumours and using the movement of the peritoneal fluid to establish metastases in the peritoneal cavity. Current therapies do not directly target metastatic dissemination, a significant contributor to the aggressiveness of OC. Therefore, there is a need for the validation of chemotherapeutic targets that reduce proliferation and metastasis to improve OC survival rates.

Myotonic Dystrophy Kinase-related Cdc-42 Binding Kinase a (MRCKa) is an attractive OC chemotherapeutic target due to its roles in tumour cell motility, survival, and proliferation. Inhibition of MRCKa activity reduced the viability of ovarian carcinoma in 2D and in 3D spheroids and reduced cell migration in vitro, suggesting that its inhibition could also block invasion and metastasis. 

Mass spectrometry was used to characterize MRCKa signaling pathways, which identified the Guanine Nucleotide Factor-Human 1 (GEF-H1) as a major MRCKa interactor. 

To determine how the interaction of MRCKa and GEF-H1 might contribute to OC, reciprocal co-immunoprecipitations were conducted to confirm the interaction and to identify the binding sites on the two proteins. The subcellular site of interaction between MRCKa and GEF-H1 is being established by proximity ligation assays. Future studies will investigate the individual and combined contributions of MRCK and GEF-H1 to cell migration and invasion by conducting 3D collective cell invasion assays. This investigation will then be expanded to organoids and in vivo models. The results of these studies will help determine how MRCKa inhibition could be effective at reducing metastatic dissemination of OC.