Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Adv Exp Med Biol. 2018;1066:299-318. doi: 10.1007/978-3-319-89512-3_15.
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.
细胞衰老，以前被认为是一种自主的肿瘤抑制机制，正在成为一种表型和效应，存在于生物体从胚胎发生到衰老衰退的整个生命周期中。衰老细胞通过其分泌表型对微环境中的多个参与者具有强大的非自主效应。衰老细胞如何通过其分泌组协调众多、有时功能相反的输出，以前尚不清楚。Notch 途径最初被确定为参与果蝇翅膀发育，最近发现它在人类癌症中具有多种作用。在这里，我们讨论了最近的发现，表明 Notch 密切参与衰老的发展，以及它如何协调衰老分泌组的组成和功能效应。我们还强调了 Notch 和 p53 之间复杂的物理和功能相互作用，这对衰老和癌症都至关重要。了解 Notch、p53 和衰老之间的相互作用，可以使我们为癌症和衰老的未来开发治疗方法。
