ArticleProceedings of the National Academy of Sciences of the United States of America2017
Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Lipid Intake and Breast Cancer Risk: Is There a Link? A New Focus and Meta-Analysis.European journal of breast health · 2022Pooled it
- Proteomic profiling of cephalic vein reveals potential biomarkers for arteriovenous fistula neointimal hyperplasia in ESRD patients.Renal failure · 2026Article
- Cholesterol Reprogramming in Acute Myeloid Leukemia: Integrating Tumor-Intrinsic Metabolism and Immune Crosstalk.Diseases (Basel, Switzerland) · 2026Review
- Dairy Processing and Breast Cancer: A Hypothesis-Generating Framework Linking Bioactive Lipid Derivatives to Epidemiological Heterogeneity.Advances in nutrition (Bethesda, Md.) · 2026Review
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Premedication with steroids in breast cancer - supportive treatment or tumour growth promotion?Magyar onkologia · 2026Review
- KDM5B cooperates with CRL4B complex to promote the tumorigenesis of ER+ breast cancer via regulating cholesterol metabolism.Cell death & disease · 2026Article
- Cancer-associated fibroblasts (CAFs) derived from MFAP2 promote CRC proliferation and metastasis while suppressing CD8Cell death & disease · 2026Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics.Scientific reports · 2025Article
- Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.Journal of translational medicine · 2025Article
- Cholestane-3β,5α,6β-triol induces cancer cell death by activating GSDME-mediated pyroptosis.Frontiers in pharmacology · 2025Article
- Cholesterol effects on the tumor immune microenvironment: from fundamental concepts to mechanisms and implications.Frontiers in oncology · 2025Review
- Determination of selected oxysterol levels, oxidative stress, and macrophage activation indicators in children and adolescents with familial hypercholesterolemia.Lipids in health and disease · 2024Article
- Cholesterol Metabolism and Urinary System Tumors.Biomedicines · 2024Review
- Oncolytic adenovirus encoding apolipoprotein A1 suppresses metastasis of triple-negative breast cancer in mice.Journal of experimental & clinical cancer research : CR · 2024Article
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- Cholesterol metabolism: a positive target to revoke the function of exhausted CAR-NK cells in tumor microenvironment.Frontiers in pharmacology · 2024Article
- Oxy- and Phytosterols as Biomarkers: Current Status and Future Perspectives.Advances in experimental medicine and biology · 2024Article
- MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B.Non-coding RNA · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer (BC) remains the primary cause of death from cancer among women worldwide. Cholesterol-5,6-epoxide (5,6-EC) metabolism is deregulated in BC but the molecular origin of this is unknown. Here, we have identified an oncometabolism downstream of 5,6-EC that promotes BC progression independently of estrogen receptor α expression. We show that cholesterol epoxide hydrolase (ChEH) metabolizes 5,6-EC into cholestane-3β,5α,6β-triol, which is transformed into the oncometabolite 6-oxo-cholestan-3β,5α-diol (OCDO) by 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2). 11βHSD2 is known to regulate glucocorticoid metabolism by converting active cortisol into inactive cortisone. ChEH inhibition and 11βHSD2 silencing inhibited OCDO production and tumor growth. Patient BC samples showed significant increased OCDO levels and greater ChEH and 11βHSD2 protein expression compared with normal tissues. The analysis of several human BC mRNA databases indicated that 11βHSD2 and ChEH overexpression correlated with a higher risk of patient death, highlighting that the biosynthetic pathway producing OCDO is of major importance to BC pathology. OCDO stimulates BC cell growth by binding to the glucocorticoid receptor (GR), the nuclear receptor of endogenous cortisol. Interestingly, high GR expression or activation correlates with poor therapeutic response or prognosis in many solid tumors, including BC. Targeting the enzymes involved in cholesterol epoxide and glucocorticoid metabolism or GR may be novel strategies to prevent and treat BC.
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