An RNAi Screen Identifies TRRAP as a Regulator of Brain Tumor-Initiating Cell Differentiation CELL STEM CELL Wurdak, H., Zhu, S., Romero, A., Lorger, M., Watson, J., Chiang, C., Zhang, J., Natu, V. S., Lairson, L. L., Walker, J. R., Trussell, C. M., Harsh, G. R., Vogels, H., Feld-Habermann, B., Orth, A. P., Miraglia, L. J., Rines, D. R., Skirboll, S. L., Schultz, P. G. 2010; 6 (1): 37-47

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer associated with a very poor prognosis. Recently, the initiation and growth of GBM has been linked to brain tumor-initiating cells (BTICs), which are poorly differentiated and share features with neural stem cells (NSCs). Here we describe a kinome-wide RNA interference screen to identify factors that control the tumorigenicity of BTICs. We identified several genes whose silencing induces differentiation of BTICs derived from multiple GBM patients. In particular, knockdown of the adaptor protein TRRAP significantly increased differentiation of cultured BTICs, sensitized the cells to apoptotic stimuli, and negatively affected cell cycle progression. TRRAP knockdown also significantly suppressed tumor formation upon intracranial BTIC implantation into mice. Together, these findings support a critical role for TRRAP in maintaining a tumorigenic, stem cell-like state.

View details for DOI 10.1016/j.stem.2009.11.002

View details for Web of Science ID 000274029700010

View details for PubMedID 20085741