ArticlePloS one2020
Transferrin receptor regulates malignancies and the stemness of hepatocellular carcinoma-derived cancer stem-like cells by affecting iron accumulation.
Article in PloS one, 2020. 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, 48 citations in OpenAlex.
- Review
- Dapagliflozin attenuates ferroptosis in diabetic nephropathy through activation of the Nrf2/HO‑1 signaling pathway.International journal of molecular medicine · 2026Article
- A proimmunotoxin nanodrug targeting AIDS-associated non-Hodgkin lymphoma.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- A fistful of iron: ferritin as a vulnerability point of the brain cancers.Cell death & disease · 2026Review
- Review
- Ferritinophagy as a Double-Edged Sword in Cancer: Novel Insights into Therapeutic Targeting of Iron-Driven Ferroptosis.Cell biochemistry and biophysics · 2026Review
- The Interplay Between Bone Biology and Iron Metabolism: Molecular Mechanisms and Clinical Implications.Biomedicines · 2026Review
- Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.Drug delivery and translational research · 2025Review
- A Robust Proteomics-Based Method for Identifying Preferred Protein Targets of Synthetic Glycosaminoglycan Mimetics.bioRxiv : the preprint server for biology · 2025Article
- Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance-from immune microenvironment crosstalk to therapeutic translation.Frontiers in immunology · 2025Review
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- Tumor-associated neutrophils in breast cancer: an angel or a devil?Frontiers in immunology · 2025Review
- Article
- Inverted U-Shaped Association of Soluble Transferrin Receptor Concentrations with Risks of Cardiovascular Diseases in Overweight Individuals: A Cross-Sectional Study.Reviews in cardiovascular medicine · 2024Article
- Preliminary Evidence of the Possible Roles of the Ferritinophagy-Iron Uptake Axis in Canine Testicular Cancer.Animals : an open access journal from MDPI · 2024Article
- FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells.Communications biology · 2024Article
- Electroacupuncture pretreatment alleviates rats cerebral ischemia-reperfusion injury by inhibiting ferroptosis.Heliyon · 2024Article
- Iron promotes ovarian cancer malignancy and advances platinum resistance by enhancing DNA repair via FTH1/FTL/POLQ/RAD51 axis.Cell death & disease · 2024Article
- Iron metabolism: backfire of cancer cell stemness and therapeutic modalities.Cancer cell international · 2024Review
- TFR1 knockdown alleviates iron overload and mitochondrial dysfunction during neural differentiation of Alzheimer's disease-derived induced pluripotent stem cells by interacting with GSK3B.European journal of medical research · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIron metabolism is essential because it plays regulatory roles in various physiological and pathological processes. Disorders of iron metabolism balance are related to various cancers, including hepatocellular carcinoma. Cancer stem-like cells (CSCs) exert critical effects on chemotherapy failure, cancer metastasis, and subsequent disease recurrence and relapse. However, little is known about how iron metabolism affects liver CSCs. Here, we investigated the expression of transferrin receptor 1 (TFR1) and ferroportin (FPN), two iron importers, and an upstream regulator, iron regulatory protein 2 (IRP2), in liver hepatocellular carcinoma (LIHC) and related CSCs.
methodsThe expression levels of TFR1, FPN and IRP2 were analysed using the GEPIA database. CSCs were derived from parental LIHC cells cultured in serum-free medium. After TFR1 knockdown, ROS accumulation and malignant behaviours were measured. The CCK-8 assay was performed to detect cell viability after TFR1 knockdown and erastin treatment.
resultsTFR1 expression was upregulated in LIHC tissue and CSCs derived from LIHC cell lines, prompting us to investigate the roles of TFR1 in regulating CSCs. Knockdown of TFR1 expression decreased iron accumulation and inhibited malignant behaviour. Knockdown of TFR1 expression decreased reactive oxygen species (ROS) accumulation induced by erastin treatment and maintained mitochondrial function, indicating that TFR1 is critical in regulating erastin-induced cell death in CSCs. Additionally, knockdown of TFR1 expression decreased sphere formation by decreasing iron accumulation in CSCs, indicating a potential role for TFR1 in maintaining stemness.
conclusionThese findings, which revealed TFR1 as a critical regulator of LIHC CSCs in malignant behaviour and stemness that functions by regulating iron accumulation, may have implications to improve therapeutic approaches.
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