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Notch and Senescence

  • Matthew Hoare
  • Masashi Narita
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1066)

Abstract

Cellular senescence, previously thought of as an autonomous tumour suppressor mechanism, is emerging as a phenotype and effector present throughout the life of an organism from embryogenesis to senile decline. Senescent cells have powerful non-autonomous effects upon multiple players within their microenvironment mainly through their secretory phenotype. How senescent cells co-ordinate numerous, sometimes functionally contrasting outputs through their secretome had previously been unclear. The Notch pathway, originally identified for its involvement in Drosophila wing development, has more recently been found to underpin diverse effects in human cancer. Here we discuss recent findings that suggest that Notch is intimately involved in the development of senescence and how it acts to co-ordinate the composition and functional effects of the senescence secretome. We also highlight the complex physical and functional interplay between Notch and p53, critical to both senescence and cancer. Understanding the interplay between Notch, p53 and senescence could allow us develop the therapeutics of the future for cancer and ageing.

Keywords

NOTCH Senescence SASP Secretome TGF-beta Interleukins Immune surveillance RAS 

Notes

Acknowledgements

MH and MN are supported by an MRC Research Grant (MR/R010013/1). MH is supported by a CRUK Clinician Scientist Fellowship (C52489/A19924). MN is supported by a Cancer Research UK Cambridge Centre Core Grant (C14303/A17197).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUK
  2. 2.Department of Medicine, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK

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