School of Biological Sciences, Seoul National University, Seoul, South Korea.
School of Biological Sciences, Seoul National University, Seoul, South Korea.
Adv Cancer Res. 2021;150:75-112. doi: 10.1016/bs.acr.2021.01.003. Epub 2021 Feb 22.
Autophagy and cellular senescence are two potent tumor suppressive mechanisms activated by various cellular stresses, including the expression of activated oncogenes. However, emerging evidence has also indicated their pro-tumorigenic activities, strengthening the case for the complexity of tumorigenesis. More specifically, tumorigenesis is a systemic process emanating from the combined accumulation of changes in the tumor support pathways, many of which cannot cause cancer on their own but might still provide excellent therapeutic targets for cancer treatment. In this review, we discuss the dual roles of autophagy and senescence during tumorigenesis, with a specific focus on the stress support networks in cancer cells modulated by these processes. A deeper understanding of such context-dependent roles may help to enhance the effectiveness of cancer therapies targeting autophagy and senescence, while limiting their potential side effects. This will steer and accelerate the pace of research and drug development for cancer treatment.
自噬和细胞衰老都是两种强有力的肿瘤抑制机制，它们可被多种细胞应激激活，包括激活的癌基因的表达。然而，新出现的证据也表明它们具有促肿瘤发生的活性，这进一步证实了肿瘤发生的复杂性。更具体地说，肿瘤发生是一个系统过程，源于肿瘤支持途径中变化的累积，其中许多变化本身不能导致癌症，但仍然可能为癌症治疗提供极好的治疗靶点。在这篇综述中，我们讨论了自噬和衰老在肿瘤发生过程中的双重作用，特别关注这些过程调节的癌细胞中的应激支持网络。更深入地了解这种依赖于上下文的作用可能有助于提高针对自噬和衰老的癌症治疗的有效性，同时限制其潜在的副作用。这将指导和加速癌症治疗的研究和药物开发的步伐。
