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Konishi J, Yi F, Chen X, et al. Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim. Oncogene. 2009;29(4):589-96doi: 10.1038/onc.2009.366.
Konishi, J., Yi, F., Chen, X., Vo, H., Carbone, D. P., & Dang, T. P. (2010). Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim. Oncogene, 29(4), 589-96. https://doi.org/10.1038/onc.2009.366
Konishi, J, et al. "Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim." Oncogene vol. 29,4 (2010): 589-96. doi: https://doi.org/10.1038/onc.2009.366
Konishi J, Yi F, Chen X, Vo H, Carbone DP, Dang TP. Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim. Oncogene. 2010 Jan 28;29(4):589-96. doi: 10.1038/onc.2009.366. Epub 2009 Nov 02. PMID: 19881544; PMCID: PMC2813325.
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Oncogene. 2010 Jan 28;29(4):589-96. doi: 10.1038/onc.2009.366. Epub 2009 Nov 02.

Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim.

Oncogene

J Konishi, F Yi, X Chen, H Vo, D P Carbone, T P Dang

Affiliations

  1. Division of Hematology and Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

PMID: 19881544 PMCID: PMC2813325 DOI: 10.1038/onc.2009.366

Abstract

Notch signaling is a highly conserved pathway important for normal embryonic development and cancer. We previously demonstrated a role for Notch3 in lung cancer pathogenesis. Notch3 inhibition resulted in tumor apoptosis and growth suppression. In vitro, these effects were enhanced when the epidermal growth factor receptor (EGFR) pathway was also inhibited, suggesting significant cross-talk between the two pathways. How Notch3 and epidermal growth factor receptor-mitogen-activated protein kinase (EGFR-MAPK) pathways cooperate in modulating apoptosis is not yet known. In this study, we provide evidence that Notch3 regulates Bim, a BH-3-only protein, via MAPK signaling. Furthermore, loss of Bim expression prevents tumor apoptosis induced by Notch3 inhibition. Using gamma-secretase inhibitor and erlotinib in a xenograft model, Bim induction and tumor inhibition were observed to be enhanced compared with either agent alone, consistent with our previous observation of significant synergism between Notch and EGFR-ras-MAPK signaling. Thus, our data support the hypothesis that Notch3 not only has a crucial role in lung cancer through regulating apoptosis, but also cooperates with the EGFR-MAPK pathway in modulating Bim.

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