The TROY Receptor is Overexpressed in Human Glioblastoma Multiforme and Fosters Glioma Cell Migration and Tumor Cell Survival
Drake, Kelsey L.1,2; Tran, Nhan L.2; Ennis, Matthew J.2,3; Armstrong; Brock A.2; Auther, Caitlin2; McDonough, Wendy S.2; and Berens, Michael E.2
1School of Life Sciences, Arizona State University, Tempe, AZ; 2Cancer and Cell Biology Division; Translational Genomics Research Institute, Phoenix, AZ; 3Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ
Glial tumors progress to malignant grades by heightened proliferation and relentless dispersion into normal brain. Understanding genetic and biochemical processes that foster these behaviors is likely to reveal specific and effective targets for therapeutic intervention. We have identified TROY / TNFRSF19 as a novel transmembrane receptor that is overexpressed in glioblastoma multiforme. TROY is a member of the tumor necrosis factor receptor (TNFR) superfamily. Unlike the classical TNFR members, TROY lacks a death domain but possesses a single TRAF binding domain. The interaction of TROY and TRAF proteins has been shown to promote cell survival via members of the Rho GTPases and NF_B pathway. Our data show that levels of TROY mRNA expression correlate with glial tumor grade; among malignant gliomas, TROY expression correlates inversely with overall patient survival. Additionally, migrating glioma cells in vitro and invading glioma cells in vivo express high levels of TROY mRNA and harbor an abundance of TROY protein product. Depletion of TROY expression by siRNA reduces glioma cell migration and invasion. These findings suggest that TROY participates in biochemical pathways that influence glioma cell motility and invasion.