Department of Pathophysiology, Graduate School of Medicine, Osaka City University, Japan.
Research Institute for Microbial Diseases, Osaka University, Japan.
FEBS J. 2023 Mar;290(5):1348-1361. doi: 10.1111/febs.16381. Epub 2022 Feb 20.
Cellular senescence refers to a state of irreversible cell cycle arrest that can be induced by various cellular stresses and is known to play a pivotal role in tumour suppression. While senescence-associated growth arrest can inhibit the proliferation of cancer-prone cells, the altered secretory profile of senescent cells, termed the senescence-associated secretory phenotype, can contribute to the microenvironment that promotes tumour development. Although the senescence-associated secretory phenotype and its effects on tumorigenesis are both highly context dependent, mechanisms underlying such diversity are becoming better understood, thereby allowing the creation of new strategies to effectively target the senescence-associated secretory phenotype and senescent cells for cancer therapy. In this review, we discuss the current knowledge on cellular senescence and the senescence-associated secretory phenotype to develop a structural understanding of their roles in the tumour microenvironment and provide perspectives for future research, including the possibility of senotherapy for the treatment of cancer.
细胞衰老指的是一种不可逆的细胞周期停滞状态,它可以由各种细胞应激诱导,并且被认为在肿瘤抑制中发挥关键作用。虽然衰老相关的生长停滞可以抑制癌症易感细胞的增殖,但衰老细胞改变的分泌特征,称为衰老相关分泌表型,可能有助于促进肿瘤发展的微环境。尽管衰老相关分泌表型及其对肿瘤发生的影响都高度依赖于背景,但对这种多样性背后的机制的理解正在不断加深,从而为有效靶向衰老相关分泌表型和衰老细胞以进行癌症治疗创造了新的策略。在这篇综述中,我们讨论了细胞衰老和衰老相关分泌表型的最新知识,以对它们在肿瘤微环境中的作用建立结构理解,并为未来的研究提供了视角,包括衰老治疗用于癌症治疗的可能性。