Department of Biochemistry and Convergence Medical Sciences and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 527-27, Republic of Korea.
Department of Biochemistry and Convergence Medical Sciences and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 527-27, Republic of Korea.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188565. doi: 10.1016/j.bbcan.2021.188565. Epub 2021 May 13.
Autophagy is a highly conserved metabolic process involved in the degradation of intracellular components including proteins and organelles. Consequently, it plays a critical role in recycling metabolic energy for the maintenance of cellular homeostasis in response to various stressors. In cancer, autophagy either suppresses or promotes cancer progression depending on the stage and cancer type. Epithelial-mesenchymal transition (EMT) and cancer metastasis are directly mediated by oncogenic signal proteins including SNAI1, SLUG, ZEB1/2, and NOTCH1, which are functionally correlated with autophagy. In this report, we discuss the crosstalk between oncogenic signaling pathways and autophagy followed by possible strategies for cancer treatment via regulation of autophagy. Although autophagy affects EMT and cancer metastasis, the overall signaling pathways connecting cancer progression and autophagy are still illusive. In general, autophagy plays a critical role in cancer cell survival by providing a minimum level of energy via self-digestion. Thus, cancer cells face nutrient limitations and challenges under stress during EMT and metastasis. Conversely, autophagy acts as a potential cancer suppressor by degrading oncogenic proteins, which are essential for cancer progression, and by removing damaged components such as mitochondria to enhance genomic stability. Therefore, autophagy activators or inhibitors represent possible cancer therapeutics. We further discuss the regulation of autophagy-dependent degradation of oncogenic proteins and its functional correlation with oncogenic signaling pathways, with potential applications in cancer therapy.
自噬是一种高度保守的代谢过程，涉及到细胞内成分的降解，包括蛋白质和细胞器。因此，它在响应各种应激源时对回收代谢能以维持细胞内稳态起着关键作用。在癌症中，自噬要么抑制要么促进癌症的进展，这取决于癌症的阶段和类型。上皮-间充质转化（EMT）和癌症转移直接由致癌信号蛋白介导，包括 SNAI1、SLUG、ZEB1/2 和 NOTCH1，它们与自噬在功能上相关。在本报告中，我们讨论了致癌信号通路与自噬之间的串扰，以及通过调节自噬来治疗癌症的可能策略。虽然自噬影响 EMT 和癌症转移，但连接癌症进展和自噬的总体信号通路仍然难以捉摸。总的来说，自噬通过自我消化提供最低水平的能量来促进癌细胞的存活。因此，癌细胞在 EMT 和转移过程中会面临营养限制和应激挑战。相反，自噬通过降解对癌症进展至关重要的致癌蛋白，以及通过去除受损的线粒体等成分来增强基因组稳定性，从而作为一种潜在的癌症抑制因子发挥作用。因此，自噬激活剂或抑制剂可能成为癌症治疗的方法。我们进一步讨论了依赖自噬的致癌蛋白降解的调节及其与致癌信号通路的功能相关性，并探讨了其在癌症治疗中的潜在应用。
