Unmasking senescence: context-dependent effects of SASP in cancer.,Nature Reviews Cancer

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Unmasking senescence: context-dependent effects of SASP in cancer.
Nature Reviews Cancer ( IF 72.5 ) Pub Date : 2019-06-24 , DOI: 10.1038/s41568-019-0156-2
Douglas V Faget ₁ , Qihao Ren ₁ , Sheila A Stewart _{1,

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Affiliation

Cellular senescence plays a critical role in tumorigenesis. Once thought of as a tissue culture artefact by some researchers, senescence is now a major field of study. Although there are common molecular mechanisms that enforce the growth arrest that characterizes the phenotype, the impact of senescence is varied and can, in some instances, have opposite effects on tumorigenesis. It has become clearer that the cell of origin and the tissue in question dictate the impact of senescence on tumorigenesis. In this Review, we unravel this complexity by focusing on how senescence impacts tumorigenesis when it arises within incipient tumour cells versus stromal cells, and how these roles can change in different stages of disease progression. In addition, we highlight the diversity of the senescent phenotype and its functional output beyond growth arrest: the senescence-associated secretory phenotype (SASP). Fortunately, a number of new genetic and pharmacologic tools have been developed that are now allowing the senescence phenotype to be parsed further.

中文翻译：

揭露衰老：SASP在癌症中的背景依赖性作用。

细胞衰老在肿瘤发生中起关键作用。曾经被一些研究人员认为是组织培养的人工制品，衰老现在是一个主要的研究领域。尽管存在常见的分子机制可以强制表现表型的生长停滞，但是衰老的影响却是多种多样的，并且在某些情况下可能对肿瘤的发生产生相反的影响。越来越清楚的是，起源细胞和相关组织决定了衰老对肿瘤发生的影响。在这篇综述中，我们通过关注衰老如何在肿瘤细胞与基质细胞之间发生时如何影响肿瘤发生以及这些作用如何在疾病进展的不同阶段发生变化来阐明这种复杂性。此外，我们着重介绍了衰老表型的多样性及其在生长停滞之外的功能输出：衰老相关的分泌表型（SASP）。幸运的是，已经开发了许多新的遗传和药理学工具，现在可以进一步解析衰老表型。

更新日期：2019-06-24

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