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

doi:10.1038/onc.2011.615

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 journal › Article › peer-review

56 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 language	English
Pages (from-to)	4698-4708
Number of pages	11
Journal	Oncogene
Volume	31
Issue number	44
DOIs	https://doi.org/10.1038/onc.2011.615
State	Published - 1 Nov 2012
Externally published	Yes

Keywords

EGFR
Mcl-1
Notch1
apoptosis
glioblastoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/onc.2011.615

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

@article{4351c762ee794b529fce8fa2168a05cd,

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

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.",

keywords = "EGFR, Mcl-1, Notch1, apoptosis, glioblastoma",

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

year = "2012",

month = nov,

day = "1",

doi = "10.1038/onc.2011.615",

language = "English",

volume = "31",

pages = "4698--4708",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "44",

}

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

TY - JOUR

T1 - Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1

AU - Fassl, A.

AU - Tagscherer, K. E.

AU - Richter, J.

AU - Berriel Diaz, M.

AU - Alcantara Llaguno, S. R.

AU - Campos, B.

AU - Kopitz, J.

AU - Herold-Mende, C.

AU - Herzig, S.

AU - Schmidt, M. H.H.

AU - Parada, L. F.

AU - Wiestler, O. D.

AU - Roth, W.

PY - 2012/11/1

Y1 - 2012/11/1

N2 - 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.

AB - 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.

KW - EGFR

KW - Mcl-1

KW - Notch1

KW - apoptosis

KW - glioblastoma

UR - http://www.scopus.com/inward/record.url?scp=84869084740&partnerID=8YFLogxK

U2 - 10.1038/onc.2011.615

DO - 10.1038/onc.2011.615

M3 - Article

C2 - 22249262

AN - SCOPUS:84869084740

SN - 0950-9232

VL - 31

SP - 4698

EP - 4708

JO - Oncogene

JF - Oncogene

IS - 44

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this