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靶向胃肠道癌铁蛋白自噬:从分子机制到意义。

Targeted ferritinophagy in gastrointestinal cancer: from molecular mechanisms to implications.

机构信息

Department of Medical Laboratory, Shandong Second Medical University, Weifang, 261053, People's Republic of China.

Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China.

出版信息

Arch Toxicol. 2024 Jul;98(7):2007-2018. doi: 10.1007/s00204-024-03745-y. Epub 2024 Apr 11.


DOI:10.1007/s00204-024-03745-y
PMID:38602537
Abstract

Gastrointestinal cancer is a significant global health burden, necessitating the development of novel therapeutic strategies. Emerging evidence has highlighted the potential of targeting ferritinophagy as a promising approach for the treatment of gastrointestinal cancer. Ferritinophagy is a form of selective autophagy that is mediated by the nuclear receptor coactivator 4 (NCOA4). This process plays a crucial role in regulating cellular iron homeostasis and has been implicated in various pathological conditions, including cancer. This review discusses the molecular mechanisms underlying ferritinophagy and its relevance to gastrointestinal cancer. Furthermore, we highlight the potential therapeutic implications of targeting ferritinophagy in gastrointestinal cancer. Several approaches have been proposed to modulate ferritinophagy, including small molecule inhibitors and immunotherapeutic strategies. We discuss the advantages and challenges associated with these therapeutic interventions and provide insights into their potential clinical applications.

摘要

胃肠道癌症是全球范围内的重大健康负担,需要开发新的治疗策略。新出现的证据强调了靶向铁蛋白自噬作为治疗胃肠道癌症的一种有前途的方法的潜力。铁蛋白自噬是一种由核受体共激活因子 4 (NCOA4) 介导的选择性自噬形式。该过程在调节细胞内铁稳态方面起着至关重要的作用,并与包括癌症在内的各种病理状况有关。本综述讨论了铁蛋白自噬的分子机制及其与胃肠道癌症的相关性。此外,我们强调了靶向胃肠道癌症中铁蛋白自噬的潜在治疗意义。已经提出了几种调节铁蛋白自噬的方法,包括小分子抑制剂和免疫治疗策略。我们讨论了这些治疗干预措施的优缺点,并提供了对其潜在临床应用的见解。

相似文献

[1]
Targeted ferritinophagy in gastrointestinal cancer: from molecular mechanisms to implications.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Nrf2/UBE3B protects against acute lung injury by inhibiting ferritinophagy through the ubiquitination of NCOA4.

Biol Direct. 2025-7-16

[2]
Ferritinophagy: a possible new iron-related metabolic target in canine osteoblastic osteosarcoma.

Front Vet Sci. 2025-3-24

[3]
SH3GL1-activated FTH1 inhibits ferroptosis and confers doxorubicin resistance in diffuse large B-cell lymphoma.

Clin Transl Med. 2025-3

[4]
CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside.

Mol Cancer. 2024-10-23

本文引用的文献

[1]
β-caryophyllene oxide induces apoptosis and inhibits proliferation of A549 lung cancer cells.

Med Oncol. 2023-5-26

[2]
PTEN-induced kinase PINK1 supports colorectal cancer growth by regulating the labile iron pool.

J Biol Chem. 2023-5

[3]
ATM orchestrates ferritinophagy and ferroptosis by phosphorylating NCOA4.

Autophagy. 2023-7

[4]
NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8.

Sci Adv. 2023-2-3

[5]
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis.

Int J Mol Sci. 2022-12-27

[6]
Ferritinophagy, a form of autophagic ferroptosis: New insights into cancer treatment.

Front Pharmacol. 2022-10-21

[7]
Mitophagy: A novel perspective for insighting into cancer and cancer treatment.

Cell Prolif. 2022-12

[8]
β-Caryophyllene oxide inhibits metastasis by downregulating MMP-2, p-p38 and p-ERK in human fibrosarcoma cells.

J Food Biochem. 2022-12

[9]
NCOA4 drives ferritin phase separation to facilitate macroferritinophagy and microferritinophagy.

J Cell Biol. 2022-10-3

[10]
Pumping Iron: Ferritinophagy Promotes Survival and Therapy Resistance in Pancreatic Cancer.

Cancer Discov. 2022-9-2

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