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Crosstalk of Notch with p53 and p63 in cancer growth control

Nature Reviews Cancer volume 9, pages 587–595 (2009)Cite this article

Abstract

Understanding the complexity of cancer depends on an elucidation of the underlying regulatory networks, at the cellular and intercellular levels and in their temporal dimension. This Opinion article focuses on the multilevel crosstalk between the Notch pathway and the p53 and p63 pathways. These two coordinated signalling modules are at the interface of external damaging signals and control of stem cell potential and differentiation. Positive or negative reciprocal regulation of the two pathways can vary with cell type and cancer stage. Therefore, selective or combined targeting of the two pathways could improve the efficacy and reduce the toxicity of cancer therapies.

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Figure 1: The Notch signalling module.
Figure 2: The p53 signalling module.
Figure 3: Notch and p53 control.
Figure 4: Crosstalk between p63 and Notch.
Figure 5: EGFR–p53–Notch: an integrated switch between tumour cell differentiation and apoptosis.

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Acknowledgements

I thank C. Brisken and C. Missero for careful reading of the manuscript and J. Aster and I. Screpanti for useful feedback. I apologize to authors whose work was not directly quoted owing to space limitations and the complexity involved. This work was supported by US National Institutes of Health grants AR054856 and AR39190 the Swiss National Foundation and a grant from the European Union (Epistem, Sixth Framework Programme, LSHB-CT-2005-019067).

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  1. G. Paolo Dotto is at the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland and at the Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Maine, 02129, USA. gian-paolo.dotto@unil.ch,

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Dotto, G. Crosstalk of Notch with p53 and p63 in cancer growth control. Nat Rev Cancer 9, 587–595 (2009). https://doi.org/10.1038/nrc2675

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