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自噬和癌症中的自噬相关途径。

Autophagy and autophagy-related pathways in cancer.

机构信息

Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.

MRC Institute of Genetics & Cancer, The University of Edinburgh, Edinburgh, UK.

出版信息

Nat Rev Mol Cell Biol. 2023 Aug;24(8):560-575. doi: 10.1038/s41580-023-00585-z. Epub 2023 Mar 2.

Abstract

Maintenance of protein homeostasis and organelle integrity and function is critical for cellular homeostasis and cell viability. Autophagy is the principal mechanism that mediates the delivery of various cellular cargoes to lysosomes for degradation and recycling. A myriad of studies demonstrate important protective roles for autophagy against disease. However, in cancer, seemingly opposing roles of autophagy are observed in the prevention of early tumour development versus the maintenance and metabolic adaptation of established and metastasizing tumours. Recent studies have addressed not only the tumour cell intrinsic functions of autophagy, but also the roles of autophagy in the tumour microenvironment and associated immune cells. In addition, various autophagy-related pathways have been described, which are distinct from classical autophagy, that utilize parts of the autophagic machinery and can potentially contribute to malignant disease. Growing evidence on how autophagy and related processes affect cancer development and progression has helped guide efforts to design anticancer treatments based on inhibition or promotion of autophagy. In this Review, we discuss and dissect these different functions of autophagy and autophagy-related processes during tumour development, maintenance and progression. We outline recent findings regarding the role of these processes in both the tumour cells and the tumour microenvironment and describe advances in therapy aimed at autophagy processes in cancer.

摘要

维持蛋白质内稳和细胞器完整与功能对于细胞内稳和细胞活力至关重要。自噬是介导各种细胞货物递送至溶酶体进行降解和再循环的主要机制。大量研究表明自噬在疾病防治中具有重要的保护作用。然而,在癌症中,自噬在预防早期肿瘤发展与维持和代谢适应已建立和转移的肿瘤方面似乎具有相反的作用。最近的研究不仅解决了自噬在肿瘤细胞中的内在功能,还研究了自噬在肿瘤微环境和相关免疫细胞中的作用。此外,还描述了各种不同于经典自噬的自噬相关途径,它们利用自噬机制的一部分,可能有助于恶性疾病的发生。越来越多的证据表明自噬和相关过程如何影响癌症的发生和发展,有助于指导基于抑制或促进自噬来设计抗癌治疗的努力。在这篇综述中,我们讨论和剖析了自噬和自噬相关过程在肿瘤发生、维持和进展中的这些不同功能。我们概述了这些过程在肿瘤细胞和肿瘤微环境中的作用的最新发现,并描述了针对癌症中自噬过程的治疗进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb3/9980873/c8d6c4468108/41580_2023_585_Fig1_HTML.jpg

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