Off the Clock: the Non-canonical Roles of Cyclin-Dependent Kinases in Neural and Glioma Stem Cell Self-Renewal

Ling Kai Shih, Subhas Mukherjee, Daniel J. Brat*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Glioma stem cells (GSCs) are thought to drive growth and therapy resistance in glioblastoma (GBM) by “hijacking” at least a subset of signaling pathways active in normal neural stem cells (NSCs). Though the origins of GSCs still remain elusive, uncovering the mechanisms of self-renewing division and cell differentiation in normal NSCs has shed light on their dysfunction in GSCs. However, the distinction between self-renewing division pathways utilized by NSC and GSC becomes critical when considering options for therapeutically targeting signaling pathways that are specifically active or altered in GSCs. It is well-established that cyclin-dependent kinases (CDKs) regulate the cell cycle, yet more recent studies have shown that CDKs also play important roles in the regulation of neuronal survival, metabolism, differentiation, and self-renewal. The intimate relationship between cell cycle regulation and the cellular programs that determine self-renewing division versus cell differentiation is only beginning to be understood, yet seems to suggest potential differential vulnerabilities in GSCs. In this timely review, we focus on the role of CDKs in regulating the self-renewal properties of normal NSCs and GSCs, highlighting novel opportunities to therapeutically target self-renewing signaling pathways specifically in GBM.

Original languageEnglish (US)
Pages (from-to)6805-6816
Number of pages12
JournalMolecular Neurobiology
Volume59
Issue number11
DOIs
StatePublished - Nov 2022

Keywords

  • Cyclin-Dependent Kinase
  • Glioblastoma
  • Glioma
  • Glioma Stem Cell
  • Neural Stem Cell
  • Self-Renewal

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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