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Notch and Senescence.

Accepted version
Peer-reviewed

Type

Book chapter

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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.

Description

Title

Notch and Senescence.

Keywords

Immune surveillance, Interleukins, NOTCH, RAS, SASP, Secretome, Senescence, TGF-beta, Aging, Animals, Cellular Senescence, Drosophila Proteins, Drosophila melanogaster, Humans, Neoplasms, Receptors, Notch, Signal Transduction, Tumor Suppressor Protein p53

Is Part Of

Advances in Experimental Medicine and Biology

Book type

Publisher

Springer International Publishing

ISBN

978-3-319-89511-6
Sponsorship
Cancer Research UK (19924)
Medical Research Council (MR/R010013/1)
Cancer Research UK (A19924)