Palladin Regulates Invadopodia Formation in Glioblastoma

Abstract

Glioblastoma multiforme (GBM), also referred to as glioblastoma is a rapidly dividing glioma that develops from astrocytes and oligodendrocytes (glial cells that nourish the brain). GBM can also be classified as a grade IV astrocytoma, which represents the most invasive, rapidly growing, and metastatic type of glial tumors. Our lab has been primarily interested in identifying and studying pathways relevant to the progression of this disease through which we recently determined that hypoxia and EGF stimulation contribute to VEGF expression via the differential regulation of the PI3K/Rho-GTPase and MAPK signaling pathways. Palladin is a relatively novel actin-associated phosphoprotein that has been reported to be implicated in a variety of cancers such as pancreatic adenocarcinoma and ductal carcinoma of the breast. It has also been reportedly involved in the development of invadopodia, dorsal ruffles, podosomes, focal adhesions, and has been shown to be involved in regulating the expression of the Rho-GTPases, Cdc42 and Rac1. More recently, palladin has been shown to alter actin dynamics in podocytes as well as replace the Arp2/3 complex during Listeria infections, contributing to the assembly of actin-based structures. In this study, we used a palladin knockdown model in order to assess invadopodia formation in glioblastoma cell line U87. The results show an increase in invadopodia as seen by TKS4 and TKS5 staining as well as a decrease in Cdc42 activity following palladin knockdown. We have also been able to demonstrate a novel role for palladin in the expression of Rac1. This study serves to characterize palladin within the context of invadopodia formation and as such we have been able to identify potential crosstalk between palladin and Rho GTPases such as Cdc42 and Rac1.