Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Acta Pharmacol Sin. 2018 Oct;39(10):1553-1558. doi: 10.1038/aps.2017.198. Epub 2018 Apr 5.
Oncogene-induced cellular senescence (OIS) is a complex program that is triggered in response to aberrant activation of oncogenic signaling. Initially, OIS was thought to be a barrier to malignant transformation because of its suppression on cell proliferation. Later studies showed that senescence induced by oncogenes can also promote the initiation and development of cancer. The opposing effects of OIS occur through different combinations of downstream effectors as well as the interplay of senescent cells and the microenvironment, such as senescence-associated inflammation. Here, we review the common features and molecular mechanisms underlying OIS and the interaction between senescent cells and the microenvironment. We propose that targeting senescent cells may have a beneficial therapeutic effect during the treatment of cancer.
癌基因诱导的细胞衰老(OIS)是一种复杂的程序,它是对致癌信号异常激活的反应而被触发的。最初,由于其对细胞增殖的抑制作用,OIS 被认为是恶性转化的障碍。后来的研究表明,癌基因诱导的衰老也可以促进癌症的发生和发展。OIS 的相反作用是通过不同的下游效应子组合以及衰老细胞与微环境(如衰老相关炎症)的相互作用来实现的。在这里,我们回顾了 OIS 的共同特征和分子机制,以及衰老细胞与微环境之间的相互作用。我们提出,针对衰老细胞可能在癌症治疗中有有益的治疗效果。