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自噬与肿瘤干细胞之间的串扰:分子机制与转化意义。

Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications.

机构信息

Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.

Shenyang Clinical Medical Research Center for Diagnosis, Treatment and Health Management of Early Digestive Cancer, Shenyang, 110032, China.

出版信息

Cell Death Dis. 2023 Jul 8;14(7):409. doi: 10.1038/s41419-023-05929-3.


DOI:10.1038/s41419-023-05929-3
PMID:37422448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10329683/
Abstract

Cancer stem cells(CSCs) play a key role in regulating tumorigenesis, progression, as well as recurrence, and possess typical metabolic characteristics. Autophagy is a catabolic process that can aid cells to survive under stressful conditions such as nutrient deficiency and hypoxia. Although the role of autophagy in cancer cells has been extensively studied, CSCs possess unique stemness, and their potential relationship with autophagy has not been fully analyzed. This study summarizes the possible role of autophagy in the renewal, proliferation, differentiation, survival, metastasis, invasion, and treatment resistance of CSCs. It has been found that autophagy can contribute to the maintenance of CSC stemness, facilitate the tumor cells adapt to changes in the microenvironment, and promote tumor survival, whereas in some other cases autophagy acts as an important process involved in the deprivation of CSC stemness thus leading to tumor death. Mitophagy, which has emerged as another popular research area in recent years, has a great scope when explored together with stem cells. In this study, we have aimed to elaborate on the mechanism of action of autophagy in regulating the functions of CSCs to provide deeper insights for future cancer treatment.

摘要

癌症干细胞(CSCs)在调节肿瘤发生、进展以及复发方面发挥着关键作用,并且具有典型的代谢特征。自噬是一种分解代谢过程,可以帮助细胞在营养缺乏和缺氧等应激条件下存活。尽管自噬在癌细胞中的作用已经得到了广泛的研究,但 CSCs 具有独特的干性,其与自噬的潜在关系尚未被充分分析。本研究总结了自噬在 CSCs 的更新、增殖、分化、存活、转移、侵袭和治疗耐药性方面的可能作用。已经发现,自噬有助于维持 CSC 的干性,使肿瘤细胞适应微环境的变化,并促进肿瘤的存活,而在其他一些情况下,自噬作为一个重要的过程,参与剥夺 CSC 的干性,从而导致肿瘤的死亡。近年来,作为另一个热门研究领域的线粒体自噬,与干细胞一起探索具有很大的前景。在本研究中,我们旨在阐述自噬在调节 CSCs 功能中的作用机制,为未来的癌症治疗提供更深入的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dd9/10329683/e1c6a886c133/41419_2023_5929_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dd9/10329683/e085bfbf095c/41419_2023_5929_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dd9/10329683/e1c6a886c133/41419_2023_5929_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dd9/10329683/e085bfbf095c/41419_2023_5929_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dd9/10329683/e1c6a886c133/41419_2023_5929_Fig2_HTML.jpg

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Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications.

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引用本文的文献

[1]
Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.

Cell Death Dis. 2025-9-1

[2]
E2F1-autophagy-ALDH1A1 axis enhances self-renewal and drug resistance of lung cancer stem-like cells in a p53-dependent manner.

J Exp Clin Cancer Res. 2025-8-30

[3]
Mitochondrial metabolic reprogramming in colorectal cancer: mechanisms of resistance and future clinical interventions.

Cell Death Discov. 2025-8-9

[4]
Targeting Cancer Cell Fate: Apoptosis, Autophagy, and Gold Nanoparticles in Treatment Strategies.

Curr Issues Mol Biol. 2025-6-14

[5]
Regulation of Stemness by NR1D2 in Colorectal Cancer.

Biomedicines. 2025-6-18

[6]
In silico-based analysis and in vitro experiments identify SIGMAR1 as a potential marker of putative lung cancer stem cells.

Discov Oncol. 2025-4-26

[7]
Multifaceted roles of OCT4 in tumor microenvironment: biology and therapeutic implications.

Oncogene. 2025-5

[8]
Long-term adaptation of lymphoma cell lines to hypoxia is mediated by diverse molecular mechanisms that are targetable with specific inhibitors.

Cell Death Discov. 2025-2-18

[9]
Identification of gastric cancer stem cells with CD44 and Lgr5 double labelling and their initial roles on gastric cancer malignancy and chemotherapy resistance.

Cell Biol Toxicol. 2024-12-21

[10]
Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.

Cancer Cell Int. 2024-12-18

本文引用的文献

[1]
CLU (clusterin) promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells.

Autophagy. 2023-8

[2]
Steatosis in metabolic diseases: A focus on lipolysis and lipophagy.

Biomed Pharmacother. 2023-4

[3]
Short peptide domains of the Wnt inhibitor sFRP4 target ovarian cancer stem cells by neutralizing the Wnt β-catenin pathway, disrupting the interaction between β-catenin and CD24 and suppressing autophagy.

Life Sci. 2023-3-1

[4]
NDP52 acts as a redox sensor in PINK1/Parkin-mediated mitophagy.

EMBO J. 2023-3-1

[5]
Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells.

EMBO Rep. 2023-2-6

[6]
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Nat Rev Mol Cell Biol. 2023-3

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Cold Spring Harb Perspect Biol. 2023-1-3

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Chaperone-Mediated Autophagy in Neurodegenerative Diseases: Molecular Mechanisms and Pharmacological Opportunities.

Cells. 2022-7-20

[9]
Mitophagy in Alzheimer's disease: Molecular defects and therapeutic approaches.

Mol Psychiatry. 2023-1

[10]
PDGF signaling inhibits mitophagy in glioblastoma stem cells through N-methyladenosine.

Dev Cell. 2022-6-20

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