ArticleNature communications2021
Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
239 citing papers in PubMed, 4 syntheses or guidelines pooled it, 330 citations in OpenAlex.
- Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Effects of different exercise prescription parameters on metabolic and inflammatory biomarkers in cancer patients: a systematic review, meta-analysis, and meta-regression.Frontiers in immunology · 2025Pooled it
- Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).International journal of oncology · 2024Pooled it
- Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024Pooled it
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review).International journal of molecular medicine · 2026Review
- Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cancer-associated adipocytes: metabolic reprogramming, crosstalk and therapeutic implications in tumor progression.Signal transduction and targeted therapy · 2026Review
- Survival phenotypes and lipid metabolic responses to DHAV-3 infection in Pekin duck hybrids with differential resistance.Poultry science · 2026Article
- The role of ferroptosis in the pathogenesis and treatment of breast cancer.Journal of translational medicine · 2026Review
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- LMAN2 promotes breast cancer progression and deduces cell sensitivity to doxorubicin through stearoyl-CoA desaturase.Breast cancer research : BCR · 2026Article
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Glucose starvation induces fumarate hydratase succinylation and inhibits ferroptosis to maintain colon cancer cell proliferation.Cell death & disease · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Article
- Cholesterol as a metabolic integrator of oncogenic signaling, immune evasion, and therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Ascites protects against ferroptosis and enables the peritoneal growth of ovarian cancer.Nature communications · 2026Article
- Revealing the Potential Associations of Mutation-Related Genes with Lymph Node Metastasis in Gallbladder Cancer Through Transcriptome and Exome Sequencing.Biomedicines · 2026Article
- Lipophilic Statins Deplete GPX4 to Promote Ferroptosis and Sensitize Cancer Cells to Immune Checkpoint Blockade.Molecular cancer therapeutics · 2026Article
179 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. We show that resistance to ferroptosis is a feature of metastatic cells and further demonstrate that GPX4 knockdown attenuates the enhanced tumorigenic and metastatic activity of 27HC resistant cells. These findings highlight the general importance of ferroptosis in tumor growth and metastasis and suggest that dyslipidemia/hypercholesterolemia impacts cancer pathogenesis by selecting for cells that are resistant to ferroptotic cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.