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CRISPR screen reveals SOX2 as a critical regulator of CD133 and cellular stress response in glioblastoma

Neil Savage1,2, Etienne Danis3,4, Chirayu R Chokshi1,2

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.

Scientific Reports
|October 16, 2025
PubMed

Insights

Glioblastoma stem cells (GSCs) survival is linked to SOX2, which controls PROM1. This finding offers new strategies to overcome therapy resistance in glioblastoma (GBM) treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma (GBM) presents significant treatment challenges.
  • Glioblastoma stem cells (GSCs), marked by CD133, drive tumor aggressiveness and therapy resistance.

Purpose of the Study:

  • To investigate the regulatory mechanisms of CD133 dynamics in glioblastoma.
  • To identify key factors influencing glioblastoma stem cell survival and resistance to treatment.

Main Methods:

  • Utilized a CRISPR-Cas9 functional screen to analyze CD133 regulation.
  • Investigated the role of SOX2 in controlling PROM1 gene expression.

Main Results:

  • Identified SOX2 as a critical regulator of the PROM1 gene.
  • Demonstrated that SOX2-PROM1 axis influences glioblastoma stem cell response to chemoradiation stress.

Conclusions:

  • SOX2 plays a pivotal role in glioblastoma stem cell survival and therapeutic resistance.
  • Targeting the SOX2-PROM1 pathway presents a potential strategy to overcome glioblastoma treatment resistance.

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