Squelching glioblastoma stem cells by targeting REST for proteasomal degradation

Peisu Zhang, Justin D. Lathia, William A. Flavahan, Jeremy N. Rich, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCFβ-TrCP. Reduced TRF2 binding to REST, and increased SCFβ-TrCP activity, target REST for proteasomal degradation and thereby inhibit cancer stem cell proliferation. Neurological side effects of treatments that target REST and TRF2 may be less severe than conventional brain tumor treatments because postmitotic neurons do not express REST and have relatively stable telomeres.

Original languageEnglish (US)
Pages (from-to)559-565
Number of pages7
JournalTrends in Neurosciences
Volume32
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Squelching glioblastoma stem cells by targeting REST for proteasomal degradation'. Together they form a unique fingerprint.

Cite this