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

Cell Rep. 2015 Jun 23;11(11):1809-21. doi: 10.1016/j.celrep.2015.05.027. Epub 2015 Jun 11.


Glioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cdc20 Proteins / genetics
  • Cdc20 Proteins / metabolism*
  • Cells, Cultured
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Mice
  • Neoplastic Stem Cells / metabolism*
  • Neurons / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction*


  • Biomarkers, Tumor
  • Cdc20 Proteins
  • SOXB1 Transcription Factors
  • CDC20 protein, human
  • Anaphase-Promoting Complex-Cyclosome