Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Oncogene. 2018 Mar;37(9):1142-1158. doi: 10.1038/s41388-017-0046-6. Epub 2017 Dec 19.
Evolutionarily conserved across eukaryotic cells, macroautophagy (herein autophagy) is an intracellular catabolic degradative process targeting damaged and superfluous cellular proteins, organelles, and other cytoplasmic components. Mechanistically, it involves formation of double-membrane vesicles called autophagosomes that capture cytosolic cargo and deliver it to lysosomes, wherein the breakdown products are eventually recycled back to the cytoplasm. Dysregulation of autophagy often results in various disease manifestations, including neurodegeneration, microbial infections, and cancer. In the case of cancer, extensive attention has been devoted to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion. In this review, while we summarize how this self-eating process is implicated at various stages of tumorigenesis, most importantly, we address the link between autophagy and hallmarks of cancer. This would eventually provide a better understanding of tumor dependence on autophagy. We also discuss how therapeutics targeting autophagy can counter various transformations involved in tumorigenesis. Finally, this review will provide a novel insight into the mutational landscapes of autophagy-related genes in several human cancers, using genetic information collected from an array of cancers.
真核细胞中普遍存在进化保守的巨自噬（以下简称自噬），它是一种靶向细胞内受损和多余的细胞蛋白、细胞器和其他细胞质成分的细胞内分解代谢过程。从机制上讲，它涉及到形成双膜囊泡，称为自噬体，自噬体捕获胞质货物并将其递送至溶酶体，其中的降解产物最终被回收回细胞质。自噬的失调通常导致各种疾病表现，包括神经退行性疾病、微生物感染和癌症。在癌症的情况下，人们广泛关注理解自噬在肿瘤抑制和肿瘤促进中的矛盾作用。在这篇综述中，我们总结了自噬过程如何在肿瘤发生的各个阶段发挥作用，最重要的是，我们探讨了自噬与癌症特征之间的联系。这将最终更好地理解肿瘤对自噬的依赖性。我们还讨论了如何通过靶向自噬的治疗来对抗肿瘤发生过程中涉及的各种转化。最后，本综述将利用从多种癌症中收集的遗传信息，提供自噬相关基因在几种人类癌症中的突变景观的新见解。
