GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
An RNAi screen identifies TRRAP as a regulator of brain tumor-initiating cell differentiation. Wurdak et al. (2010) Brain tumor-initiating cell differentiation Number of cells per colony and number of coloniesBrain tumor initiating cell lines from glioblastoma multiforme tumorsH. sapiens

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.

Screen details


Stable Id: GR00212-A
Screen title: Brain tumor-initiating cell differentiation
Assay: Number of cells per colony and number of colonies
Method: Fluorescence
Scope: Kinases
Screen type: Cell-based
Species: Homo sapiens
Biosource: Primary cells
Biomodel: Brain tumor initiating cell lines from glioblastoma multiforme tumors
Library: Genomics Institute of the Novartis Research Foundation (GNF), Human Kinome Loss-of-Function Lentiviral shRNA Library Collection
Reagent type: shRNA
Score type: Euclidean distance from control
Cutoff: > 3 standard deviations below mean distance
Notes: Author-reviewed data. Additional information about secondary screens