The Role of Cholesterol Metabolism and Its Regulation in Tumor Development

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2025-03-27 DOI:10.1002/cam4.70783

Yongmei Wu, Wenqian Song, Min Su, Jing He, Rong Hu, Youbo Zhao

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Abstract

Background

Within the tumor microenvironment, tumor cells undergo metabolic reprogramming of cholesterol due to intrinsic cellular alterations and changes in the extracellular milieu. Furthermore, cholesterol reprogramming within this microenvironment influences the immune landscape of tumors, facilitating immune evasion and consequently promoting tumorigenesis. These biological changes involve modifications in numerous enzymes associated with cholesterol uptake and synthesis, including NPC1L1, SREBP, HMGCR, SQLE, and PCSK9.

Review

This review systematically summarizes the role of cholesterol metabolism and its associated enzymes in cancer progression, examines the mechanisms through which dysregulation of cholesterol metabolism affects immune cells within the tumor microenvironment, and discusses recent advancements in cancer therapies that target cholesterol metabolism.

Conclusion

Targeting cholesterol metabolism-related enzymes can inhibit tumor growth, reshape immune landscapes, and rejuvenate antitumor immunity, offering potential therapeutic avenues in cancer treatment.

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胆固醇代谢及其调控在肿瘤发生中的作用

在肿瘤微环境中，由于内在细胞改变和细胞外环境的变化，肿瘤细胞经历胆固醇代谢重编程。此外，在这个微环境中胆固醇重编程影响肿瘤的免疫景观，促进免疫逃避，从而促进肿瘤发生。这些生物学变化涉及许多与胆固醇摄取和合成相关的酶的修饰，包括NPC1L1、SREBP、HMGCR、SQLE和PCSK9。本综述系统总结了胆固醇代谢及其相关酶在癌症进展中的作用，探讨了胆固醇代谢失调影响肿瘤微环境中免疫细胞的机制，并讨论了针对胆固醇代谢的癌症治疗的最新进展。结论靶向胆固醇代谢相关酶可以抑制肿瘤生长，重塑免疫景观，恢复抗肿瘤免疫，为癌症治疗提供了潜在的治疗途径。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.