ArticleJournal of experimental & clinical cancer research : CR2024
Augmented ERO1α upon mTORC1 activation induces ferroptosis resistance and tumor progression via upregulation of SLC7A11.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis 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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- ERO1α as a Potential Drug Target for Breast Cancer: A Systematic Review of Current Evidence.International journal of molecular sciences · 2025Pooled it
- TRAPPC4 Promotes GPX4 Stability to Drive Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Unlocking ferroptosis heterogeneity: ATF4 versus SREBF transcriptional programs.Cell death discovery · 2026Article
- Multi-omics analysis identifies GINS1 as a prognostic biomarker in lung adenocarcinoma, linked to macrophage polarization and tumor cell survival.Discover oncology · 2026Article
- ALKBH5 aggravates scarring after glaucoma surgery via mCell death and differentiation · 2026Article
- Review
- Correlations of P53, SLC7A11, CD3+ T cells, and CD8+ T cells with pathological features and prognosis in endometrial carcinoma: Insights from an Asian cohort.Journal of medical biochemistry · 2026Article
- Molecular mechanisms in endometriosis: linking JAK/STAT pathway, ferroptosis, and microbial dysbiosis.Molecular biology reports · 2026Review
- Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha-Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer.Biomedicines · 2026Review
- SLC16A1 Activates the STAT3/SLC7A11 Pathway to Mediate Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma.Oncology research · 2026Article
- mTOR signaling in cholangiocarcinoma: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- TPI1 promotes malignant progression and ferroptosis resistance in head and neck squamous cell carcinoma.Frontiers in genetics · 2026Article
- Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer.Cancers · 2025Review
- Targeting ferroptosis: a novel pathway in oral, oropharyngeal, hypopharyngeal, and laryngeal cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Inhibition of DDR1 potentiates carbon ion radiotherapy by promoting ferroptosis and immunogenic death in head and neck squamous cell carcinoma.Journal of translational medicine · 2025Article
- PRMT1-Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ferroptosis as a therapeutic vulnerability in MDM2 inhibition in dedifferentiated liposarcoma.Oncology letters · 2025Article
- The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.Biomolecules · 2025Review
- Research progress on ferroptosis in head and neck squamous cell carcinoma.Journal of molecular histology · 2025Review
- JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases.Cancer cell international · 2025Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood.
methodsEndoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT-PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models.
resultsERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors.
conclusionsThe ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors.
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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.