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Cytokine Signaling in Development, Homeostasis and Disease

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: 20 February 2025 | Viewed by 1067

Special Issue Editor

Special Issue Information

Dear Colleagues,

Life is complex! To generate a fully formed organism requires intricate developmental processes, many of which continue into adulthood. In addition, there is a need for on-going maintenance and responsiveness to external conditions. This relies on multiple layers of regulation to ensure it occurs in an appropriate manner.

Cytokines represent a key mechanism by which cells communicate to one another during development and as part of various homeostatic mechanisms, with a particular important role in blood and immune cells. They are produced by a variety of cells and act via specific cell-surface receptors on target cells to initiate intracellular signaling pathways that rapidly alter cell functions. Perturbation of cytokine signaling has also been identified in a number of pathological states.

This Special Issue showcases cytokine signaling with a strong focus on its function in development, homeostasis and disease.

Prof. Dr. Alister C. Ward
Guest Editor

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Keywords

  • cytokine signaling
  • development
  • homeostasis
  • disease

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Published Papers (1 paper)

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Research

18 pages, 9505 KiB  
Article
MDH2 Promotes Hepatocellular Carcinoma Growth Through Ferroptosis Evasion via Stabilizing GPX4
by Wenjia Yu, Yingping Li, Chengchang Gao, Donglin Li, Liangjie Chen, Bolei Dai, Haoying Yang, Linfen Han, Qinqin Deng and Xueli Bian
Int. J. Mol. Sci. 2024, 25(21), 11604; https://doi.org/10.3390/ijms252111604 - 29 Oct 2024
Cited by 1 | Viewed by 657
Abstract
The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal [...] Read more.
The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal 3 (RSL3), a compound known to cause ferroptosis. MDH2 knock-down enhances RSL3-induced intracellular reactive oxygen species, free iron ions and lipid per-oxides levels, leading to HCC ferroptotic cell death which is rescued by ferrostatin-1 and iron chelator deferiprone. Importantly, the inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity dependent on glutathione peroxidase 4 (GPX4), an enzyme responsible for scavenging lipid peroxides, which is stabilized by MDH2 in HCC. The protein expressions of MDH2 and GPX4 are positively correlated with each other in HCC cell lines. Furthermore, through our UALCAN website analysis, we found that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combi-nation with ferroptosis inducers for the treatment of HCC. Full article
(This article belongs to the Special Issue Cytokine Signaling in Development, Homeostasis and Disease)
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