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Title: Pharmacological Inhibition of REST in Glioblastoma
Introduction: RE1-silencing transcription factor (REST) silences neuronal differentiation genes. Its overexpression in an aggressive subset of gliomas is believed to support the enhanced tumor-initiating and self-renewal capacities of glioblastoma cancer stem cells (GSCs). Therefore, REST knockdown is hypothesized to inhibit tumor growth and recurrence. Because REST, as a large protein, is difficult to target directly with small molecules, our study focuses on knocking down REST by inhibiting one of its regulatory enzymes, small C-terminal domain phosphatase 1 (SCP1). Dephosphorylation of REST by SCP1 protects the former from degradation; consequently, SCP1 inhibition with an experimental drug, T62, is expected to reduce REST protein levels. This REST knockdown is hypothesized to induce the expression of neuronal differentiation genes, thereby forcing differentiation of GSCs and making them more vulnerable to standard treatments. We begin our study by validating patient-derived GSC lines and subsequently testing the efficacy of T62 drug in these cells. Our work supports an effort to understand various molecular pathologies of GBM and its intrinsic GSCs in order to develop novel therapeutic strategies.  more » « less
Award ID(s):
1757885
NSF-PAR ID:
10138564
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
2019 BMES Conference Proceedings - REU Abstract Accepted Poster
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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