A graphical journey through iron metabolism, microRNAs, and hypoxia in ferroptosis

Fuhrmann, Dominik C.; Brüne, Bernhard

doi:10.1016/j.redox.2022.102365

Cited by 38 publications

(21 citation statements)

References 50 publications

(55 reference statements)

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“…Strategies aimed at limiting the spread of glioblastoma cells into healthy brain, potentially through manipulating iron metabolism, could yield improvements to patient outcomes. Furthermore, iron may impact other features of glioblastoma tumor biology such as induction of hypoxic responses [48][49][50], immune function [51], and susceptibility to ferroptosis [34,35] that may offset its contribution to cell proliferation. Our findings shed light on the largely uncharacterized role of iron in glioblastoma cell migration and demonstrate the need for further investigation into the role of iron in cancer cell and tumor microenvironment biology.…”

Section: Discussionmentioning

confidence: 99%

“…While iron’s ability to promote cell proliferation at sub-toxic concentrations has indeed been well documented, other impacts of iron on cancer cell biology, including cell migration, have been less thoroughly characterized. In recent years the double-edged nature of iron in cancer biology has begun to be appreciated with discoveries such as ferroptosis, a form of iron-dependent cell death [34,35], demonstrating that iron may potentially have favorable roles in cancer treatment. Here we add to the literature describing iron’s numerous impacts on cancer cell biology by demonstrating that iron alters the ability of glioblastoma cells to migrate – a deadly feature that enables these cells to diffusely spread into healthy brain and generate recurrent disease.…”

Section: Discussionmentioning

confidence: 99%

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Iron Inhibits Glioblastoma Cell Migration and Polarization

Shenoy

Kheirabadi

Ataie

et al. 2022

Preprint

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Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate - a key question especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. Bioinformatic analysis of CDC42 mRNA revealed a potential iron-responsive element that may contribute to the regulation of CDC42 by iron. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Iron Inhibits Glioblastoma Cell Migration and Polarization

Shenoy

Kheirabadi

Ataie

et al. 2022

Preprint

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“…Ferroptosis is a non-apoptotic form of cell death that depends on iron-mediated lipid free radical formation and accumulation ( Peng et al, 2023 ). It is characterized by increased lipid peroxidation (LPO) leading to cell death through disturbing membrane integrity ( Fuhrmann and Brune, 2022 ). Ferroptosis can be inhibited by glutathione peroxidase 4 (GPX4) and glutathione (GSH), which are key regulators for protecting cells from LPO ( Wang M. P. et al, 2022 ).…”

Section: Functions Of N6-methyladenosine Modification In Central Nerv...mentioning

confidence: 99%

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

Tian

Mao

Zhang

2022

Front. Cell. Neurosci.

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Central nervous system (CNS) injuries, including traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and ischemic stroke, are the most common cause of death and disability around the world. As the most common modification on ribonucleic acids (RNAs), N6-methyladenosine (m6A) modification has recently attracted great attentions due to its functions in determining the fate of RNAs through changes in splicing, translation, degradation and stability. A large number of studies have suggested that m6A modification played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that m6A modification could improve neurological impairment, inhibit apoptosis, suppress inflammation, reduce pyroptosis and attenuate ferroptosis in CNS injuries via different molecules including phosphatase and tensin homolog (PTEN), NLR family pyrin domain containing 3 (NLRP3), B-cell lymphoma 2 (Bcl-2), glutathione peroxidase 4 (GPX4), and long non-coding RNA (lncRNA). Therefore, m6A modification showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the role of m6A modification in CNS injuries. Hence, on the basis of these properties and effects, m6A modification may be developed as therapeutic agents for CNS injury patients.

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“…Although drug screening based on 3D cells is still in its infancy, its excellent physiological properties make drug screening based on 3D cell models have broad application prospects (Castro et al, 2021;Pamarthy and Sabaawy 2021). Ferroptosis-related agents are rapidly evolving in developing new drugs and are particularly effective in inhibiting several types of cancer (Fuhrmann and Brune 2022). Ferroptosis is an iron-dependent cell death mode that differs from traditional programmed cell death, such as apoptosis, pyroptosis, and autophagy (Zhang and Liu 2022).…”

Section: Introductionmentioning

confidence: 99%

The three-dimension preclinical models for ferroptosis monitoring

Meng

Sun

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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As a new programmed cell death process, ferroptosis has shown great potential and uniqueness in experimental and treatment-resistant cancer models. Currently, the main tools for drug research targeting ferroptosis are tumor cells cultured in vitro and tumor models established in rodents. In contrast, increasing evidence indicates that reactivity may differ from modifications in mice or humans in the process of drug screening. With the blossoming of 3D culture technology, tumor organoid culture technology has gradually been utilized. Compared with traditional 2D culture and tumor tissue xenotransplantation, tumor organoids have a significantly higher success rate. They can be cultured quickly and at a lower cost, which is convenient for gene modification and large-scale drug screening. Thus, combining 3D cell culture technology, drug monitoring, and ferroptosis analysis is necessary to develop the impact of ferroptosis-related agents in tumor treatment.

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A graphical journey through iron metabolism, microRNAs, and hypoxia in ferroptosis

Cited by 38 publications

References 50 publications

Iron Inhibits Glioblastoma Cell Migration and Polarization

Iron Inhibits Glioblastoma Cell Migration and Polarization

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

The three-dimension preclinical models for ferroptosis monitoring

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