Department of Biochemistry and Convergence Medical Sciences, Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu 527-27, Korea.
Cells. 2019 Feb 6;8(2):129. doi: 10.3390/cells8020129.
Autophagy, an intracellular degradation process, is essential for maintaining cell homeostasis by removing damaged organelles and proteins under various conditions of stress. In cancer, autophagy has conflicting functions. It plays a key role in protecting against cancerous transformation by maintaining genomic stability against genotoxic components, leading to cancerous transformation. It can also promote cancer cell survival by supplying minimal amounts of nutrients during cancer progression. However, the molecular mechanisms underlying how autophagy regulates the epithelial-to-mesenchymal transition (EMT) and cancer metastasis are unknown. Here, we show that starvation-induced autophagy promotes Snail (SNAI1) degradation and inhibits EMT and metastasis in cancer cells. Interestingly, SNAI1 proteins were physically associated and colocalized with LC3 and SQSTM1 in cancer cells. We also found a significant decrease in the levels of EMT and metastatic proteins under starvation conditions. Furthermore, knockdown inhibited autophagy-induced SNAI1 degradation in the cytoplasm, which was associated with a decrease in SNAI1 nuclear translocation. Moreover, cancer cell invasion and migration were significantly inhibited by starvation-induced autophagy. These findings suggest that autophagy-dependent SNAI1 degradation could specifically regulate EMT and cancer metastasis during tumorigenesis.
自噬是一种细胞内降解过程，对于在各种应激条件下清除受损的细胞器和蛋白质，维持细胞内稳态至关重要。在癌症中，自噬具有双重作用。它通过维持基因组稳定性来对抗遗传毒性成分，从而防止癌变，从而在保护免受癌变转化方面发挥关键作用。它还可以通过在癌症进展过程中提供少量营养物质来促进癌细胞存活。然而，自噬如何调节上皮-间充质转化（EMT）和癌症转移的分子机制尚不清楚。在这里，我们表明饥饿诱导的自噬促进了 Snail（SNAI1）的降解，并抑制了癌细胞中的 EMT 和转移。有趣的是，在癌细胞中，SNAI1 蛋白与 LC3 和 SQSTM1 发生物理关联和共定位。我们还发现，在饥饿条件下，EMT 和转移蛋白的水平显著下降。此外，抑制自噬诱导的 SNAI1 降解会导致细胞质中 SNAI1 核转位减少。此外，饥饿诱导的自噬显著抑制了癌细胞的侵袭和迁移。这些发现表明，自噬依赖性 SNAI1 降解可以在肿瘤发生过程中特异性调节 EMT 和癌症转移。
