The Crosstalk Between Palladin and Rho GTPases

Abstract

Glioblastoma Multiforme (GBM) is the most aggressive and malignant primary brain tumor, characterized by recurrence and poor prognosis with 1-year survival rate. The spread of this rapidly growing neoplasm into adjacent areas of the brain is extremely dependent on cell adhesion and invasion. These processes are specifically mediated by signaling pathways that activate Rho GTPases and their downstream effectors. Palladin, an actin-binding phosphoprotein, contributes to cell adhesion and invasion in different types of cancers through modulating Rho GTPases. Palladin is also involved in the development of focal adhesion and the formation of invadopodia through regulating the expression of RhoA, Cdc42 and Rac1. In this study, we aimed to investigate the crosstalk between palladin and Rho GTPases in regulating cell adhesion and invasion. A Palladin knockdown model was used to study the effect of this protein on cell adhesion and invasion, as well as invadopodia formation in Glioblastoma SNB-19 cells. The results show that Palladin positively regulates cell adhesion through RhoA expression. We also demonstrated that palladin negatively regulates invasion and invadopodia formation through observing an increase in TKS4 and TKS5 invadopodia markers. Therefore, we have been able to study the crosstalk between Palladin and Rho GTPases in regulating adhesion and invasion of GBM.