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A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

Diane D Mao1, Amit D Gujar1, Tatenda Mahlokozera2

  • 1Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

Cell Reports
|June 16, 2015
PubMed

Insights

The mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives glioblastoma stem-like cell (GSC) invasiveness and self-renewal. Targeting this CDC20-APC/SOX2 axis may offer new glioblastoma treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Glioblastoma (GBM) contains stem-like cells (GSCs) resistant to therapy.
  • Understanding GSC mechanisms is crucial for developing new GBM treatments.

Purpose of the Study:

  • To investigate the role of CDC20-anaphase-promoting complex (CDC20-APC) in GSC biology.
  • To identify therapeutic targets for glioblastoma.

Main Methods:

  • Studied patient tumor-derived GSCs.
  • Utilized CDC20 knockdown and overexpression experiments.
  • Employed an orthotopic xenograft model in vivo.
  • Investigated the interaction with SOX2.

Main Results:

  • CDC20-APC promotes GSC invasiveness and self-renewal.
  • CDC20 knockdown inhibited GSC tumor formation in vivo.
  • CDC20 overexpression enhanced GSC tumor formation.
  • CDC20-APC regulates GSC properties via SOX2.

Conclusions:

  • A CDC20-APC/SOX2 signaling axis controls key GSC biological properties.
  • This axis represents a potential therapeutic target for glioblastoma.

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