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Ferroptosis and Cuproptosis: Mechanism and Crosstalk in Cancer, Neurodegeneration, and Metabolic Syndrome

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 387

Special Issue Editor

Dr. Rosanna Squitti

E-Mail Website
Guest Editor
Dipartimento di Scienze di Laboratorio, Sezione Ricerca e Sviluppo, Ospedale Fatebenefratelli Isola Tiberina–Gemelli Isola, Via di Ponte Quattro Capi 39, 00186 Roma, Italy
Interests: neurodegenerative disorders; colorectal cancer; essential metals; Alzheimer’s disease; psychiatric disorders; copper; iron; zinc
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This special issue explores the emerging concepts of ferroptosis and cuproptosis, two distinct forms of regulated cell death, and their roles in cancer, neurodegeneration, and metabolic syndrome. The scope of the special issue spans the mechanisms underlying ferroptosis and cuproptosis, their interconnection, and their crosstalk in various diseases. Topics covered include but are not limited to, Alzheimer's disease, psychiatric disorders, and colorectal cancer, highlighting how these forms of cell death contribute to disease progression and potential therapeutic strategies. By examining the interplay of iron and copper metabolism in disease pathogenesis, this special issue provides a comprehensive view of how ferroptosis and cuproptosis impact cellular function and contribute to various pathological conditions, opening new avenues for targeted treatment.

Suitable topics include, but are not limited to: Alzheimer's disease, psychiatric disorders, and colorectal cancer.

You may choose our Joint Special Issue in Biomolecules.

Dr. Rosanna Squitti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ferroptosis
  • cuproptosis
  • Alzheimer's disease
  • colorectal cancer
  • neurodegeneration
  • metabolic syndrome
  • regulated cell death
  • iron metabolism
  • copper metabolism
  • psychiatric disorders

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Published Papers (1 paper)

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Research

17 pages, 1687 KiB  
Article
Sex Hormones and Iron-Related Biomarkers Associate with EMT Features and Tumor Stage in Colorectal Cancer: A Serum- and Tissue-Based Analysis
by Rosanna Squitti, Anastasia De Luca, Altea Severino, Gianluca Rizzo, Federica Marzi, Luca Emanuele Amodio, Gabriella Vicano, Antonio Focaccio, Vincenzo Tondolo and Mauro Rongioletti
Int. J. Mol. Sci. 2025, 26(11), 5163; https://doi.org/10.3390/ijms26115163 - 28 May 2025
Viewed by 252
Abstract
Sex steroid hormones and systemic iron metabolism are emerging as modulators of colorectal cancer (CRC) development and progression. However, information linking systemic factors to tumor characteristics and epithelial–mesenchymal transition (EMT) is limited, particularly in a sex-specific context. We measured serum levels of sex [...] Read more.
Sex steroid hormones and systemic iron metabolism are emerging as modulators of colorectal cancer (CRC) development and progression. However, information linking systemic factors to tumor characteristics and epithelial–mesenchymal transition (EMT) is limited, particularly in a sex-specific context. We measured serum levels of sex hormones [testosterone, estradiol, progesterone, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Carcinoembryonic antigen (CEA)] and iron-related biomarkers (iron, transferrin, ferritin, % transferrin saturation, ceruloplasmin, and the ceruloplasmin/transferrin ratio) in 82 CRC patients and 31 healthy controls. EMT-related proteins [mediator of ErbB2-driven cell motility 1 (MEMO1), E-cadherin, fibronectin, vimentin, and vinculin] were quantified by Western blotting in tumor and adjacent normal mucosa. Non-parametric tests and Spearman correlations were applied, stratified by sex and corrected for age and anemia where appropriate. Progesterone levels were significantly lower in male CRC patients (median 0.17 ng/mL vs. 0.20 ng/mL, p = 0.04) and higher in female patients (0.17 ng/mL vs. 0.10 ng/mL, p = 0.0077) compared with controls. The iron-related biomarkers indicated a pattern of iron deficiency, including in non-anemic patients, with reduced % transferrin saturation (p < 0.01) and an elevated ceruloplasmin/transferrin ratio (p = 0.02). Correlations were found between iron status, tumor stage, and hormonal levels. Progesterone correlated with EMT protein expression in healthy mucosa (e.g., fibronectin in females: ρ = 0.567, p = 0.014; vimentin in males: ρ = −0.446, p = 0.007), but not in tumor tissue. In the healthy mucosa of male patients, ceruloplasmin/transferrin correlated with MEMO1 (ρ = 0.419, p = 0.04), vinculin (ρ = 0.299, p = 0.041), and vimentin (ρ = 0.394, p = 0.07); transferrin levels inversely correlated with MEMO1 expression (ρ = −0.392, p = 0.032), and vimentin showed a positive correlation with serum iron (ρ = 0.350, p = 0.043). Furthermore, fibronectin expression inversely correlated with iron in the sole tumor tissue of female patients (ρ = −0.366, p = 0.040). These findings support the role of sex hormones and iron metabolism in CRC biology, suggesting that EMT might be accompanied by altered iron uptake and redox remodeling, which can enhance cellular motility and the metastatic potential. Full article
(This article belongs to the Special Issue Ferroptosis and Cuproptosis: Mechanism and Crosstalk in Cancer, Neurodegeneration, and Metabolic Syndrome)
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