ArticleNature metabolism2021
Hepcidin sequesters iron to sustain nucleotide metabolism and mitochondrial function in colorectal cancer epithelial cells.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- The Role of Iron Chelation Therapy in Colorectal Cancer: A Systematic Review on Its Mechanisms and Therapeutic Potential.Cancer medicine · 2025Pooled it
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Iron, inflammation, and intestinal tumors: the crucial triad in colorectal cancer progression and therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Gallium-Containing Agents for Tumor Diagnosis and Therapy: Current Status and Future Prospects.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Labile iron pool dynamics do not drive ferroptosis in colorectal cancer cells.The Journal of biological chemistry · 2026Article
- Fatty acids in the tumor microenvironment reprogram neutrophils to induce immunosuppression via adenosine.bioRxiv : the preprint server for biology · 2026Article
- Integrative genomic profiling of iron homeostasis predicts clinical outcomes and identifies HAMP/hepcidin as a therapeutic target in colorectal cancer.Cell & bioscience · 2026Article
- Epithelial HO-1 regulates iron availability and promotes colonic tumorigenesis in a context-dependent manner.JCI insight · 2026Article
- Patient-specific pharmacogenomics demonstrates xCT as predictive therapeutic target in colon cancer with possible implications in tumor connectivity.Molecular oncology · 2026Article
- Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Intestine-Specific Ferroportin Ablation Rescues from Systemic Iron Overload in Mice.Nutrients · 2026Article
- Iron and metabolic rewiring in cancer.Oncogenesis · 2026Review
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Competitive Binding of UBA52 and HOPX Modulates β-catenin Stability in Colorectal Cancer in the Context of High-Iron Intake.International journal of biological sciences · 2026Article
- Iron regulation by Sirtuins 1 & 2 and their therapeutic modulation by Sirtinol.Frontiers in pharmacology · 2026Review
- Curcumin Analogues Trigger HMOX1-Mediated Ferroptosis to Halt Endometrial Cancer Growth.bioRxiv : the preprint server for biology · 2025Article
- Serum hepcidin concentration is lower in advanced stages of sporadic colorectal cancer.Biochemia medica · 2025Article
- Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Colorectal cancer (CRC) requires massive iron stores, but the complete mechanisms by which CRC modulates local iron handling are poorly understood. Here, we demonstrate that hepcidin is activated ectopically in CRC. Mice deficient in hepcidin specifically in the colon tumour epithelium, compared with wild-type littermates, exhibit significantly diminished tumour number, burden and size in a sporadic model of CRC, whereas accumulation of intracellular iron by deletion of the iron exporter ferroportin exacerbates these tumour parameters. Metabolomic analysis of three-dimensional patient-derived CRC tumour enteroids indicates a prioritization of iron in CRC for the production of nucleotides, which is recapitulated in our hepcidin/ferroportin mouse CRC models. Mechanistically, our data suggest that iron chelation decreases mitochondrial function, thereby altering nucleotide synthesis, whereas exogenous supplementation of nucleosides or aspartate partially rescues tumour growth in patient-derived enteroids and CRC cell lines in the presence of an iron chelator. Collectively, these data suggest that ectopic hepcidin in the tumour epithelium establishes an axis to sequester iron in order to maintain the nucleotide pool and sustain proliferation in colorectal tumours.
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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.