ArticleCell communication and signaling : CCS2024
Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- 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
- Iron Metabolism in the Colorectal Tumor Microenvironment: From Preneoplastic Lesions to Cancer Progression.International journal of molecular sciences · 2026Review
- Integrative genomic profiling of iron homeostasis predicts clinical outcomes and identifies HAMP/hepcidin as a therapeutic target in colorectal cancer.Cell & bioscience · 2026Article
- Mitochondrial homeostasis meets novel programmed cell death: crosstalk mechanisms underlying cardiovascular diseases progression.Cell communication and signaling : CCS · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting Iron Regulatory Protein 2 in Tumor-associated Macrophages Activates Antitumor Immunity in NSCLC via Modulating SphK1-PD-L1 Axis.International journal of biological sciences · 2026Article
- Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- USP5 regulates ferroptosis in colorectal cancer by targeting the YBX3/SLC7A11 axis through lysosomal degradation.Cell death & disease · 2025Article
- Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.Nature aging · 2025Article
- Review
- Targeting iron regulatory protein 2 (IRP2) to disrupt iron metabolism enhances radiosensitivity through mitochondrial dysfunction in breast cancer cells.Cell death discovery · 2025Article
- Integrative genomic and single-cell framework identifies druggable targets for colorectal cancer precision therapy.Frontiers in immunology · 2025Article
- The Impact of Iron on Cancer-Related Immune Functions in Oncology: Molecular Mechanisms and Clinical Evidence.Cancers · 2024Review
- Correction: Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.Cell communication and signaling : CCS · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
backgroundDysregulation of iron metabolism is implicated in malignant transformation, cancer progression, and therapeutic resistance. Here, we demonstrate that iron regulatory protein 2 (IRP2) preferentially regulates iron metabolism and promotes tumor growth in colorectal cancer (CRC).
methodsIRP2 knockdown and knockout cells were generated using RNA interference and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 methodologies, respectively. Cell viability was evaluated using both CCK-8 assay and cell counting techniques. Furthermore, IRP2 inhibition was determined by surface plasmon resonance (SPR) and RNA immunoprecipitation (IP). The suppressive effects of IRP2 were also corroborated in both organoid and mouse xenograft models, providing a comprehensive validation of IRP2's role.
resultsWe have elucidated the role of IRP2 as a preferential regulator of iron metabolism, actively promoting tumorigenesis within CRC. Elevated levels of IRP2 expression in patient samples are correlated with diminished overall survival, thereby reinforcing its potential role as a prognostic biomarker. The functional suppression of IRP2 resulted in a pronounced delay in tumor growth. Building on this proof of concept, we have developed IRP2 inhibitors that significantly reduce IRP2 expression and hinder its interaction with iron-responsive elements in key iron-regulating proteins, such as ferritin heavy chain 1 (FTH1) and transferrin receptor (TFRC), culminating in iron depletion and a marked reduction in CRC cell proliferation. Furthermore, these inhibitors are shown to activate the AMPK-ULK1-Beclin1 signaling cascade, leading to cell death in CRC models.
conclusionsCollectively, these findings highlight the therapeutic potential of targeting IRP2 to exploit the disruption of iron metabolism in CRC, presenting a strategic advancement in addressing a critical area of unmet clinical need.
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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.