Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1

A. Fassl, K. E. Tagscherer, J. Richter, M. Berriel Diaz, S. R. Alcantara Llaguno, B. Campos, J. Kopitz, C. Herold-Mende, S. Herzig, M. H H Schmidt, L. F. Parada, O. D. Wiestler, W. Roth

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The Notch1-mediated signaling pathway has a central role in the maintenance of neural stem cells and contributes to growth and progression of glioblastomas, the most frequent malignant brain tumors in adults. Here, we demonstrate that the Notch1 receptor promotes survival of glioblastoma cells by regulation of the anti-apoptotic Mcl-1 protein. Notch1-dependent regulation of Mcl-1 occurs cell type dependent at a transcriptional or post-translational level and is mediated by the induction of epidermal growth factor receptor (EGFR). Inhibition of the Notch1 pathway overcomes apoptosis resistance and sensitizes glioblastoma cells to apoptosis induced by ionizing radiation, the death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) or the Bcl-2/Bcl-XL inhibitor ABT-737. In conclusion, targeting Notch1 might represent a promising novel strategy in the treatment of glioblastomas.

Original languageEnglish (US)
Pages (from-to)4698-4708
Number of pages11
JournalOncogene
Volume31
Issue number44
DOIs
StatePublished - Nov 1 2012

Keywords

  • EGFR
  • Mcl-1
  • Notch1
  • apoptosis
  • glioblastoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1'. Together they form a unique fingerprint.

  • Cite this

    Fassl, A., Tagscherer, K. E., Richter, J., Berriel Diaz, M., Alcantara Llaguno, S. R., Campos, B., Kopitz, J., Herold-Mende, C., Herzig, S., Schmidt, M. H. H., Parada, L. F., Wiestler, O. D., & Roth, W. (2012). Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1. Oncogene, 31(44), 4698-4708. https://doi.org/10.1038/onc.2011.615