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Cited by 53Cancer, Lipids, and MetabolismCholesterol and Lipid MetabolismSteroid Chemistry and Biochemistry

Our evolving understanding of how 27-hydroxycholesterol influences cancer

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Ma, Liqian, Cho, Wonhwa, Nelson, Erik R.·2022·Biochemical Pharmacology
DOI 10.1016/j.bcp.2021.114621PMC PMC8611110
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Abstract

Cholesterol has been implicated in the pathophysiology and progression of several cancers now, although the mechanisms by which it influences cancer biology are just emerging. Two likely contributing mechanisms are the ability for cholesterol to directly regulate signaling molecules within the membrane, and certain metabolites acting as signaling molecules. One such metabolite is the oxysterol 27-hydroxycholesterol (27HC), which is a primary metabolite of cholesterol synthesized by the enzyme Cytochrome P450 27A1 (CYP27A1). Physiologically, 27HC is involved in the regulation of cholesterol homeostasis and contributes to cholesterol efflux through liver X receptor (LXR) and inhibition of de novo cholesterol synthesis through the insulin-induced proteins (INSIGs). 27HC is also a selective modulator of the estrogen receptors. An increasing number of studies have identified its importance in cancer progression of various origins, especially in breast cancer. In this review, we discuss the physiological roles of 27HC targeting these two nuclear receptors and the subsequent contribution to cancer progression. We describe how 27HC promotes tumor growth directly through cancer-intrinsic factors, and indirectly through its immunomodulatory roles which lead to decreased immune surveillance and increased tumor invasion. This review underscores the importance of the cholesterol metabolic pathway in cancer progression and the potential therapeutic utility of targeting this metabolic pathway.

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Authors
Ma, L., Cho, W., & Nelson, E. R.
Affiliations
  • University of Illinois Urbana-Champaign (US)
  • University of Illinois Chicago (US)
Corresponding author
Nelson, Erik R.
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2022-02
Volume
196
Pages
114621
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2021.114621
PMC
PMC8611110
OpenAlex
W3165690650
Cited by
53
References
148
Citations by year
2026: 9 · 2025: 14 · 2024: 6 · 2023: 13 · 2022: 10 · 2021: 1
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Pharmacology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA234025)
  • National Institute of General Medical Sciences (R35GM122530)
  • National Institutes of Health
  • U.S. Department of Defense (W81XWH-20-BCRP-EOHS / BC200206)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Keywords
27-hydroxycholesterol, oxysterols, cholesterol metabolism, tumor progression, CYP27A1, liver X receptor, Insig, estrogen receptor modulation, breast cancer, tumor immunosuppression, tumor invasion, cholesterol homeostasis
MeSH terms
Animals, Anticholesteremic Agents, Cholesterol, Dietary, Humans, Hydroxycholesterols, Neoplasms, Biomarkers, Tumor, Cholestanetriol 26-Monooxygenase

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