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Cancers
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The Impact of Iron Metabolism in Cancer
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The Impact of Iron Metabolism in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 8135

Special Issue Editors

Dr. Toshiaki Ohara

E-Mail Website
Guest Editor
Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
Interests: cancer stem cell; iron metabolism in tumor micro environment
Dr. Meera Nanjundan

E-Mail Website
Guest Editor
Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA
Interests: iron; ovarian cancer; endometriosis; kidney cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Iron is an essential element for the human body. However, excess iron is known to cause some kinds of cancer such as malignant mesothelioma, renal cancer, and ovarian cancer. Excess-free iron induces oxidative stress, which explains the carcinogenesis and acquisition of more malignant potential. The stemness ability of cancer is also known to be closely related with iron metabolism. Interestingly, both over oxidative stress and iron depletion induce cell death such as ferroptosis and apoptosis. This is controversial, making it more suitable for cancer therapy. Furthermore, immune cells and cancer-associated fibroblast are also affected by iron metabolism the same as cancer cells. However, the detailed mechanism and therapeutic approach remain unclear. Thus, this Special Issue aims to reveal the impact of iron metabolism in cancer and tumor, helping to conquer cancer.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: iron metabolism in cancer and tumor microenvironment, iron-related carcinogenesis and progress of malignant potential, iron control cancer therapy (such as iron chelator and ferroptosis inducer), and cancer therapy targeting mitochondria.

We look forward to receiving your contributions. 

Dr. Toshiaki Ohara
Dr. Meera Nanjundan
Guest Editors

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • iron metabolism
  • ferroptosis
  • iron chelator
  • mitochondria
  • ferric
  • ferrous
  • ROS
  • oxidative stress

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Published Papers (3 papers)

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Research

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18 pages, 2886 KiB  
Article
Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators
by Yuze Wang, Toshiaki Ohara, Yuehua Chen, Yusuke Hamada, Chunning Li, Masayoshi Fujisawa, Teizo Yoshimura and Akihiro Matsukawa
Cancers 2023, 15(2), 468; https://doi.org/10.3390/cancers15020468 - 12 Jan 2023
Cited by 6 | Viewed by 2919
Abstract
Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed [...] Read more.
Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators. Full article
(This article belongs to the Special Issue The Impact of Iron Metabolism in Cancer)
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Review

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17 pages, 1655 KiB  
Review
Environmental Determinants of Ferroptosis in Cancer
by Yasaman Setayeshpour, Yunji Lee and Jen-Tsan Chi
Cancers 2023, 15(15), 3861; https://doi.org/10.3390/cancers15153861 - 29 Jul 2023
Cited by 1 | Viewed by 2307
Abstract
Given the enormous suffering and death associated with human cancers, there is an urgent need for novel therapeutic approaches to target tumor growth and metastasis. While initial efforts have focused on the dysregulated oncogenic program of cancer cells, recent focus has been on [...] Read more.
Given the enormous suffering and death associated with human cancers, there is an urgent need for novel therapeutic approaches to target tumor growth and metastasis. While initial efforts have focused on the dysregulated oncogenic program of cancer cells, recent focus has been on the modulation and targeting of many “cancer-friendly,” non-genetic tumor microenvironmental factors, which support and enable tumor progression and metastasis. Two prominent examples are anti-angiogenesis and immunotherapy that target tumor-supporting vascularization and the immune-suppressive tumor microenvironment (TME), respectively. Lately, there has been significant interest in the therapeutic potential of ferroptosis, a natural tumor suppression mechanism that normally occurs as a result of oxidative stress, iron imbalance, and accumulation of lipid peroxides. While numerous studies have identified various cell intrinsic mechanisms to protect or promote ferroptosis, the role of various TME stress factors are also recently recognized to modulate the tumor cells’ susceptibility to ferroptosis. This review aims to compile and highlight evidence of these factors, how various TME stresses affect ferroptosis, and their implications in various stages of tumor development and expected response to ferroptosis-triggering therapeutics under development. Consequently, understanding ways to enhance ferroptosis sensitivity both intracellularly and in the TME may optimize therapeutic sensitivity to minimize or prevent tumor growth and metastasis. Full article
(This article belongs to the Special Issue The Impact of Iron Metabolism in Cancer)
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15 pages, 1119 KiB  
Review
Targeting Iron-Sulfur Clusters in Cancer: Opportunities and Challenges for Ferroptosis-Based Therapy
by Jaewang Lee and Jong-Lyel Roh
Cancers 2023, 15(10), 2694; https://doi.org/10.3390/cancers15102694 - 10 May 2023
Cited by 8 | Viewed by 2407
Abstract
Iron dysregulation is a hallmark of cancer, characterized by an overexpression of genes involved in iron metabolism and iron-sulfur cluster (ISC) biogenesis. Dysregulated iron homeostasis increases intracellular labile iron, which may lead to the formation of excess cytotoxic radicals and make it vulnerable [...] Read more.
Iron dysregulation is a hallmark of cancer, characterized by an overexpression of genes involved in iron metabolism and iron-sulfur cluster (ISC) biogenesis. Dysregulated iron homeostasis increases intracellular labile iron, which may lead to the formation of excess cytotoxic radicals and make it vulnerable to various types of regulated cell death, including ferroptosis. The inhibition of ISC synthesis triggers the iron starvation response, increasing lipid peroxidation and ferroptosis in cancer cells treated with oxidative stress-inducing agents. Various methods, such as redox operations, iron chelation, and iron replacement with redox-inert metals, can destabilize or limit ISC formation and function, providing potential therapeutic strategies for cancer treatment. Targeting ISCs to induce ferroptosis represents a promising approach in cancer therapy. This review summarizes the state-of-the-art overview of iron metabolism and ferroptosis in cancer cells, the role of ISC modulation in ferroptosis, and the potential of targeting ISCs for ferroptosis induction in cancer therapy. Further research is necessary to develop and validate these strategies in clinical trials for various cancers, which may ultimately lead to the development of novel and effective treatments for cancer patients. Full article
(This article belongs to the Special Issue The Impact of Iron Metabolism in Cancer)
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