Autophagy at the intersection of aging, senescence, and cancer

Cassidy, Liam; Narita, Masashi

doi:10.1002/1878-0261.13269

Cited by 41 publications

(18 citation statements)

References 167 publications

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“…In light of these functions, it is not surprising that autophagy has roles that protect against cancer. In the following subsections we first briefly summarize work on the roles of autophagy as a tumour suppressor mechanism that has been discussed in greater detail elsewhere [10][11][12][13][14] , to provide essential background understanding for our more detailed discussion of recent developments in the field.…”

Section: Suppression Of Tumour Developmentmentioning

confidence: 99%

Autophagy and autophagy-related pathways in cancer

Debnath

Gammoh

Ryan

2023

Nat Rev Mol Cell Biol

438

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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 Nature Reviews Molecular Cell Biology Review articleATG3 and ATG7. These proteins facilitate the lipid conjugation of the ATG8 family members (consisting of the microtubule-associated protein 1A/1B-light chain 3 (LC3) and GABARAP subfamilies), which are important during cargo recruitment and autophagosome maturation 3,4 (Fig. 1), as well as other processes that involve ATG8-lipid conjugation (see below and Supplementary Box 1). Although cargo recruitment can be non-selective, for example in nutrient-depleted cells where autophagosomes take up different cargoes to recycle crucial nutrients such as amino acids or lipids, autophagy is largely highly selective. This selectivity is facilitated by autophagy cargo receptors (ACRs) (Fig. 1 and Supplementary Box 2), which bind to specific cargoes that have been tagged for degradation via ubiquitindependent or ubiquitin-independent processes 5 . To add further to this complexity, recent studies have unravelled additional roles of ATG proteins beyond autophagosome formation, thereby expanding their functions and implications in disease 6 (Box 1). Two additional lysosomal degradation processes exist that are related to (macro) autophagy but do not require the activities of ATG proteins. These include chaperone-mediated autophagy and microautophagy, in which cargo delivery to the lysosome relies on chaperone activity and invagination of the lysosomal membrane to encapsulate cellular material, respectively 1 .Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author sel...

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Section: Suppression Of Tumour Developmentmentioning

confidence: 99%

Autophagy and autophagy-related pathways in cancer

Debnath

Gammoh

Ryan

2023

Nat Rev Mol Cell Biol

438

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“…The crosstalk between autophagy and endoplasmic reticulum stress is important in pulmonary fibrosis ( Ghavami et al, 2018 ; Maciel et al, 2018 ). Therapeutic approaches targeting autophagy have been shown to have great potential in cancer and aging ( Xia et al, 2021 ; Cassidy and Narita, 2022 ). Interestingly, studies have found that autophagy also plays an important role in IPF.…”

Section: Important Cells and Extracellular Matrix Involved In The Pat...mentioning

confidence: 99%

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Recent studies have identified the key role of crosstalk between dysregulated epithelial cells, mesenchymal, immune, and endothelial cells in IPF. In addition, genetic mutations and environmental factors (e.g., smoking) have also been associated with the development of IPF. With the recent development of sequencing technology, epigenetics, as an intermediate link between gene expression and environmental impacts, has also been reported to be implicated in pulmonary fibrosis. Although the etiology of IPF is unknown, many novel therapeutic targets and agents have emerged from clinical trials for IPF treatment in the past years, and the successful launch of pirfenidone and nintedanib has demonstrated the promising future of anti-IPF therapy. Therefore, we aimed to gain an in-depth understanding of the underlying molecular mechanisms and pathogenic factors of IPF, which would be helpful for the diagnosis of IPF, the development of anti-fibrotic drugs, and improving the prognosis of patients with IPF. In this study, we summarized the pathogenic mechanism, therapeutic targets and clinical trials from the perspective of multiple cell types, gene mutations, epigenetic and environmental factors.

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“…The role of autophagy in tumor development is complex and may depend on the stage and tissue of the tumor. Autophagy is thought to be essential for cell health, and its loss may lead to tumor damage (Cassidy & Narita, 2022). Natural products induce autophagy in NPC (Table 2).…”

Section: Regulation Of Autophagymentioning

confidence: 99%

The efficacy of natural products for the treatment of nasopharyngeal carcinoma

Ao,

Luo,

Zhang

et al. 2023

Chem Biol Drug Des

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Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long‐term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC.

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Autophagy at the intersection of aging, senescence, and cancer

Cited by 41 publications

References 167 publications

Autophagy and autophagy-related pathways in cancer

Autophagy and autophagy-related pathways in cancer

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

The efficacy of natural products for the treatment of nasopharyngeal carcinoma

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