Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Biochim Biophys Acta Mol Basis Dis. 2021 Dec 1;1867(12):166262. doi: 10.1016/j.bbadis.2021.166262. Epub 2021 Sep 1.
Autophagy refers to a ubiquitous set of catabolic pathways required to achieve proper cellular homeostasis. Aberrant autophagy has been implicated in a multitude of diseases including cancer. In this review, we highlight pioneering and groundbreaking research that centers on delineating the role of autophagy in cancer initiation, proliferation and metastasis. First, we discuss the autophagy-related (ATG) proteins and their respective roles in the de novo formation of autophagosomes and the subsequent delivery of cargo to the lysosome for recycling. Next, we touch upon the history of cancer research that centers upon ATG proteins and regulatory mechanisms that control an appropriate autophagic response and how these are altered in the diseased state. Then, we discuss the various discoveries that led to the idea of autophagy as a double-edged sword when it comes to cancer therapy. This review also briefly narrates how different types of autophagy-selective macroautophagy and chaperone-mediated autophagy, have been linked to different cancers. Overall, these studies build upon a steadfast trajectory that aims to solve the monumentally daunting challenge of finding a cure for many types of cancer by modulating autophagy either through inhibition or induction.
自噬是指一组普遍存在的分解代谢途径,对于实现适当的细胞内稳态是必需的。异常的自噬与多种疾病有关,包括癌症。在这篇综述中,我们重点介绍了开创性和突破性的研究,这些研究集中在阐明自噬在癌症的发生、增殖和转移中的作用。首先,我们讨论了与自噬相关的(ATG)蛋白及其在新形成的自噬体中的各自作用,以及随后将货物递送至溶酶体进行回收的过程。接下来,我们谈到了以 ATG 蛋白为中心的癌症研究历史,以及控制适当自噬反应的调节机制,以及这些机制在疾病状态下是如何改变的。然后,我们讨论了导致自噬在癌症治疗中成为一把双刃剑的各种发现。这篇综述还简要描述了不同类型的自噬——选择性巨自噬和伴侣介导的自噬——如何与不同的癌症有关。总的来说,这些研究建立在一个坚定的轨迹上,旨在通过抑制或诱导自噬来解决治疗多种癌症的巨大挑战。