The Power Behind the Throne: Senescence and the Hallmarks of Cancer
The Power Behind the Throne: Senescence and the Hallmarks of Cancer
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DOI：
10.1146/annurev-cancerbio-030617-050352
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Narita, Masashi
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文献类型：
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作者：
Hoare, Matthew;Narita, Masashi
细胞衰老是由各种刺激（包括致癌和其他细胞应激）触发的稳定增殖停滞状态。衰老细胞具有高度代谢活性，并通过衰老相关分泌表型（SASP）产生多种深远的非自主效应。越来越明显的是，衰老细胞可以对邻近的癌细胞和肿瘤微环境中的其他参与者（如基质、脉管系统和免疫系统）产生肿瘤抑制或促癌作用。因此，在过去十年左右的时间里，我们对衰老生物学的理解发生了巨大的飞跃，将其从一种自主的肿瘤抑制因子提升为一种复杂、动态和相互作用的表型。 “癌症标志”的概念也在这一时期演变，最新的迭代（Hanahan & Weinberg 2011）更多地关注微环境，这也许并非巧合。在这里，我们认为细胞衰老可能是癌症许多特征的生物学基础，使其成为王位背后的真正力量。
Cellular senescence is a state of stable proliferative arrest triggered by various stimuli, including oncogenic and other cellular stress. Senescent cells are highly metabolically active and have diverse and profound nonautonomous effects through the senescence-associated secretory phenotype (SASP). It has become increasingly evident that senescent cells can have tumour suppressive or pro-oncogenic effects on adjacent cancer cells and other players in the tumor microenvironment such as the stroma, vasculature, and immune system. Thus, the last decade or so has witnessed a huge leap forward in our understanding of the biology of senescence, promoting it from an autonomous tumor suppressor to a complex, dynamic, and interactive phenotype. It is perhaps not a coincidence that the concept of the "hallmarks of cancer" has also evolved during this period, with the latest iteration (Hanahan & Weinberg 2011) focusing more on the microenvironment. Here, we suggest that cellular senescence could underpin the biology of many of the hallmarks of cancer, making it the true power behind the throne.