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

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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

Fingerprint

Glioblastoma
Epidermal Growth Factor Receptor
Cell Survival
Apoptosis
Notch1 Receptor
Ligands
Neural Stem Cells
Ionizing Radiation
Brain Neoplasms
Tumor Necrosis Factor-alpha
Maintenance
Growth
Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Fassl, A., Tagscherer, K. E., Richter, J., Berriel Diaz, M., Alcantara Llaguno, S. R., Campos, B., ... 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

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

In: Oncogene, Vol. 31, No. 44, 01.11.2012, p. 4698-4708.

Research output: Contribution to journalArticle

Fassl, A, Tagscherer, KE, Richter, J, Berriel Diaz, M, Alcantara Llaguno, SR, Campos, B, Kopitz, J, Herold-Mende, C, Herzig, S, Schmidt, MHH, Parada, LF, Wiestler, OD & Roth, W 2012, 'Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1', Oncogene, vol. 31, no. 44, pp. 4698-4708. https://doi.org/10.1038/onc.2011.615
Fassl A, Tagscherer KE, Richter J, Berriel Diaz M, Alcantara Llaguno SR, Campos B et al. Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1. Oncogene. 2012 Nov 1;31(44):4698-4708. https://doi.org/10.1038/onc.2011.615
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. / Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1. In: Oncogene. 2012 ; Vol. 31, No. 44. pp. 4698-4708.
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