Small Molecule MIF Modulation Enhances Ferroptosis by Impairing DNA Repair Mechanisms Article Swipe
Deng Chen
,
Chunlong Zhao
,
Jianqiu Zhang
,
Catharina W. J. Knol
,
Angelina Osipyan
,
Nad’a Majerníková
,
Tingting Chen
,
Zhangping Xiao
,
Jeaunice Adriana
,
Andrew J. Griffith
,
Abel Soto Gamez
,
Petra E. van der Wouden
,
Robert P. Coppes
,
Amalia M. Dolga
,
Hidde J. Haisma
,
Frank J. Dekker
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202403963
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202403963
Ferroptosis is a form of regulated cell death that can be modulated by small molecules and has the potential for the development of therapeutics for oncology. Although excessive lipid peroxidation is the defining hallmark of ferroptosis, DNA damage may also play a significant role. In this study, a potential mechanistic role for MIF in homologous recombination (HR) DNA repair is identified. The inhibition or genetic depletion of MIF or other HR proteins, such as breast cancer type 1 susceptibility protein (BRCA1), is demonstrated to significantly enhance the sensitivity of cells to ferroptosis. The interference with HR results in the translocation of the tumor suppressor protein p53 to the mitochondria, which in turn stimulates the production of reactive oxygen species. Taken together, the findings demonstrate that MIF‐directed small molecules enhance ferroptosis via a putative MIF‐BRCA1‐RAD51 axis in HR, which causes resistance to ferroptosis. This suggests a potential novel druggable route to enhance ferroptosis by targeted anticancer therapeutics in the future.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/advs.202403963
- OA Status
- gold
- Cited By
- 9
- References
- 70
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4400011526
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4400011526Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/advs.202403963Digital Object Identifier
- Title
-
Small Molecule MIF Modulation Enhances Ferroptosis by Impairing DNA Repair MechanismsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-25Full publication date if available
- Authors
-
Deng Chen, Chunlong Zhao, Jianqiu Zhang, Catharina W. J. Knol, Angelina Osipyan, Nad’a Majerníková, Tingting Chen, Zhangping Xiao, Jeaunice Adriana, Andrew J. Griffith, Abel Soto Gamez, Petra E. van der Wouden, Robert P. Coppes, Amalia M. Dolga, Hidde J. Haisma, Frank J. DekkerList of authors in order
- Landing page
-
https://doi.org/10.1002/advs.202403963Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1002/advs.202403963Direct OA link when available
- Concepts
-
DNA damage, Reactive oxygen species, Cell biology, Druggability, Homologous recombination, DNA repair, Apoptosis, Programmed cell death, DNA, Suppressor, Chemistry, Biology, Cancer research, Cancer, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
9Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 7, 2024: 2Per-year citation counts (last 5 years)
- References (count)
-
70Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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