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Dysregulation of cholesterol metabolism in cancer progression

Oncogene volume 42, pages 3289–3302 (2023)Cite this article

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Abstract

Cholesterol homeostasis has been implicated in the regulation of cellular and body metabolism. Hence, deregulated cholesterol homeostasis leads to the development of many diseases such as cardiovascular diseases, and neurodegenerative diseases, among others. Recent studies have unveiled the connection between abnormal cholesterol metabolism and cancer development. Cholesterol homeostasis at the cellular level dynamically circulates between synthesis, influx, efflux, and esterification. Any dysregulation of this dynamic process disrupts cholesterol homeostasis and its derivatives, which potentially contributes to tumor progression. There is also evidence that cancer-related signals, which promote malignant progression, also regulate cholesterol metabolism. Here, we described the relationship between cholesterol metabolism and cancer hallmarks, with particular focus on the molecular mechanisms, and the anticancer drugs that target cholesterol metabolism.

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Fig. 1: Cholesterol metabolism reprogramming in cancer cells.
Fig. 2: Cancer hallmarks and their association with cholesterol metabolism.
Fig. 3: Anticancer therapeutic strategies targeting cholesterol metabolism.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81988101, 82172930, and 81830086), National Key R&D Program of China (2022YFC3401002), Beijing Municipal Commission of Health and Family Planning Project (PXM2018_026279_000005), Beijing Nova Program (Z191100001119038), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-081), Funding by Major Program of Shenzhen Bay Laboratory (S201101004), Guangdong Basic and Applied Basic Research Foundation (2019B030302012), the Fund of “San-ming” Project of Medicine in Shenzhen (No. SZSM201812088), Beijing Hospitals Authority Youth Program (QML20191104).

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Author notes

  1. These authors contributed equally: Xuesong Liu, Mengzhu Lv.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Xuesong Liu, Mengzhu Lv, Weimin Zhang & Qimin Zhan

  2. Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, Beijing, 100021, China

    Xuesong Liu, Mengzhu Lv, Weimin Zhang & Qimin Zhan

  3. Peking University International Cancer Institute, Beijing, 100191, China

    Xuesong Liu & Qimin Zhan

  4. Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, 518107, China

    Weimin Zhang & Qimin Zhan

  5. Soochow University Cancer Institute, Suzhou, 215127, China

    Qimin Zhan

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QZ, WZ, and XL conceived the idea, QZ, WZ supervised this study. XL and ML designed and produced illustrative material, and wrote the manuscript. QZ and WZ supervised and revised the manuscript. All authors approved the final version.

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Correspondence to Weimin Zhang or Qimin Zhan.

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Liu, X., Lv, M., Zhang, W. et al. Dysregulation of cholesterol metabolism in cancer progression. Oncogene 42, 3289–3302 (2023). https://doi.org/10.1038/s41388-023-02836-x

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