Abstract:
Glioblastoma multiforme (GBM), is a grade IV CNS tumor according to the World Health Organization. This glioma arises from astrocytes and oligodendrocytes leading to two different categories known as primary glioblastoma and secondary glioblastoma. Glioblastoma is known for its high invasive and metastatic properties with fast growth rates which makes it have a minimal survival percentage and slow prognosis. One of many important proteins that has been shown to be involved in invasive tumors such as pancreatic and breast cancer is palladin. Palladin contributes to cell invasion and metastasis through actin regulation in addition to regulating expression levels of some RhoGTPases. In this research, we focus on investigating the role of palladin in the regulation of invadopodia formation by knocking it down in glioma cells lines to evaluate its effect using TKS4 and TKS5 as invadopodia markers through immunofluorescence experiments. In El Sibai lab, we mostly study signaling pathways responsible for cancer cell metastasis and invasion with a focus on RhoGTPases, so we also sought to investigate if there is any interaction between palladin and RhoGTPases such as RhoA and CDC42. Our findings indicate that the knockdown of palladin results in elevated levels of invadopodia formation, as indicated by the staining of TKS4 and TKS5 proteins, and reduced activity of Cdc42. Moreover, we have uncovered a new function of palladin in regulating RhoA expression. This research provides valuable understandings into the intricate mechanisms that are responsible for the development of invadopodia in glioblastoma multiforme and facilitate metastasis and cell invasion, shedding light on the critical roles of palladin and Rho GTPases. The research has successfully characterized the function of palladin in invadopodia formation and highlighted the possible interplay between palladin and Rho GTPases, including Cdc42 and RhoA.
