Department of Biophysics and Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2616-43. doi: 10.2741/4074.
Pre-malignant tumor cells enter a state of irreversible cell cycle arrest termed senescence (cellular senescence; CS). CS is a part of the aging program and involves multiple signaling cascades and transduction mechanisms. In general, senescence can be divided into replicative senescence and premature senescence. Replicative senescence (replicative CS) has been described for all metabolically active cells that undergo a spontaneous decline in growth rate. Notably, ectopic expression of telomerase holoenzyme (hTert) can prevent replicative CS. In cancer cells, premature senescence induced by oncogenes, named oncogene-induced senescence (oncogene induced CS; OIS), play an important role in preventing the development of cancer. Oncogene induced CS can be promoted by the loss of tumor suppressor genes, such as PTEN. Additionally, other interesting mechanisms, like selective microRNA expression, epigenetic modifications, or even stress conditions, are also able to activate the senescence program. Here, we will critically review the literature on the role of senescence in preventing the development of cancer and discuss the potential of senescence modulation for generating new molecular tools that could be explored as anticancer treatments.
肿瘤前体细胞进入一种不可逆的细胞周期停滞状态，称为衰老（细胞衰老；CS）。CS 是衰老程序的一部分，涉及多个信号级联和转导机制。一般来说，衰老可分为复制性衰老和过早衰老。所有代谢活跃的细胞都会经历自发的生长速度下降，从而出现复制性衰老（replicative CS）。值得注意的是，端粒酶全酶（hTert）的异位表达可以防止复制性 CS。在癌细胞中，癌基因诱导的衰老（oncogene-induced CS；OIS），称为癌基因诱导的衰老，在预防癌症发展方面起着重要作用。OIS 可以通过肿瘤抑制基因的缺失来促进，如 PTEN。此外，其他有趣的机制，如选择性 microRNA 表达、表观遗传修饰，甚至应激条件，也能够激活衰老程序。在这里，我们将批判性地回顾衰老在预防癌症发展中的作用的文献，并讨论衰老调节产生新的分子工具的潜力，这些工具可以作为抗癌治疗进行探索。
