Abstract:
Cell metastasis is the main difference between malignant and benign tumors, and it is a main contributor to the high mortality rate of malignant cancer. Therefore, it is of great interest to study the pathways involved in the motility of cancer cells, which are regulated by the Rho family of small GTPases. This study examines the role of the Rho GTPases, RhoC and Cdc42 in 3D cell motility, mainly in the formation of actin structures termed invadopodia. RhoC was shown to play a role in both 2D and 3D cell motility; whereas, the action of Cdc42 is limited to 3D motility. We first established the formation of invadopodia through PMA stimulation. Next, our results showed that these invadopodia are Cdc42 dependent and that the inhibition of ROCK leads to the increase in invadopodia formation. It was also shown that RhoC downregulates the activation of Cdc42 which leads to the final conclusion that RhoC is active around the invadopodia structure, where it inhibits Cdc42 through the action of ROCK, allowing the invadopodia structure to become more concentrated and focused. Additionally, Palladin protein was shown to inhibit Cdc42, which may imply a crosstalk between palladin, RhoC and Cdc42 in invadopodia formation.
