The Effect of DJ-1 on Invasion and Invadopodia Formation in Glioblastoma Multiforme

Abstract

Glioblastoma multiform (GBM) is one of the most aggressive malignant brain tumors. Advances in the treatment of this cancer are limited by the infiltrating nature of the GBM cancer cells. DJ-1 is an oncogene which stimulates cell proliferation by inhibiting the tumor suppressor PTEN and leads to the subsequent activation of the PI3Kinase pathway. We have shown in the lab that DJ-1 knockdown decreases 2D cell motility of breast cancer cells. In this study, we sought to investigate the role of DJ-1 in 3D migration and invasion and particularly, in the formation of invadopodia. To this aim, we first investigated the various proteins that DJ-1 interacts with and the subsequent pathways they modulate to better understand its role in cancer. Then, we investigated how DJ-1 affects cell viability and the PI3K/PTEN pathway in glioblastoma cells. We next examined the expression and subcellular localization of DJ-1 and noted that it localizes at the invadopodia sites. Consistently, co-immunofluorescence of DJ-1 with structural proteins which regulate actin dynamics, namely, ARP2 and SH3PXD2B demonstrated a clear co-localization of DJ-1 with both markers at the invadopodia. Our results also revealed that the number of invadopodia decreases upon DJ-1 depletion.