ArticleCell death & disease2018
E4BP4 promotes thyroid cancer proliferation by modulating iron homeostasis through repression of hepcidin.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Transcription factor, E4BP4, inhibits autophagy and apoptosis in multiple myeloma and promotes the HDAC3-mediated suppression of the Beclin1 promoter to reduce dexamethasone sensitivity.Journal of translational medicine · 2026Article
- Effects of essential metals (iron, zinc, and copper) on thyroid diseases - a narrative review.Frontiers in medicine · 2026Review
- Review
- Elemental comparative analysis of 18 elements reveal distinct patterns in benign and malignant thyroid tissues.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases-A Literature Review.Nutrients · 2025Review
- AEBP1 promotes papillary thyroid cancer progression by activating BMP4 signaling.Neoplasia (New York, N.Y.) · 2024Article
- The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update.Molecular biology reports · 2024Review
- The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.Frontiers in nutrition · 2024Article
- Fe-Zn alloy, a new biodegradable material capable of reducing ROS and inhibiting oxidative stress.Regenerative biomaterials · 2024Article
- HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.British journal of cancer · 2023Review
- Review
- A new border for circadian rhythm gene NFIL3 in diverse fields of cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Interpreting Iron Homeostasis in Congenital and Acquired Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Distinctive modulation of hepcidin in cancer and its therapeutic relevance.Frontiers in oncology · 2023Review
- Prognostic Significance of Iron Metabolism Related Genes in Human Lung Adenocarcinoma.Cancer management and research · 2023Article
- Bioinformatics analysis of downstream circRNAs and miRNAs regulated by Runt-related transcription factor 1 in papillary thyroid carcinoma.Gland surgery · 2022Article
- Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity.Redox biology · 2022Article
- Nanomedicine targets iron metabolism for cancer therapy.Cancer science · 2022Review
- Elevated expression of the rhythm gene NFIL3 promotes the progression of TNBC by activating NF-κB signaling through suppression of NFKBIA transcription.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron homeostasis is critical to mammals, and dysregulation in iron homeostasis usually leads to severe disorders including various cancers. Massive hepcidin secretion is an indicator of thyroid cancer, but the molecular mechanisms responsible for this dysregulation are unknown. Hepcidin secretion from thyroid cancer cells also leads to decreased expression of the iron exporter, ferroportin (FPN), and increased intracellular iron retention, which promote cancer proliferation. In this study, we examined the role of hepcidin in thyroid cancer (TC) and the molecular bases of its signaling. Synthesis of hepcidin is regulated by the BMP4/7 agonist SOSTDC1, which was downregulated in TC; SOSTDC1 downregulation was correlated with G9a-mediated hypermethylation in its promoter. The binding of G9a to the SOSTDC1 promoter requires E4BP4, which interacts with G9a to form a multi-molecular complex that contributes to SOSTDC1 silencing. Silencing of E4BP4 or G9a has similar effects to SOSTDC1 overexpression, which suppresses secretion of hepcidin and inhibits TC cell proliferation. Furthermore, our in vivo xenograft data indicated that depletion of E4BP4 also inhibits cancer growth, reduces hepcidin secretion, and reduces G9a nuclear transportation. Iron homeostasis and tumor growth in TC may be regulated by an E4BP4-dependent epigenetic mechanism. These findings suggest a new mechanism of cellular iron dysfunction through the E4BP4/G9a/SOSTDC1/hepcidin pathway, which is an essential link in TC.
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