Small Molecule MIF Modulation Enhances Ferroptosis by Impairing DNA Repair Mechanisms
Abstract: 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.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Small Molecule MIF Modulation Enhances Ferroptosis by Impairing DNA Repair Mechanisms ; day:25 ; month:06 ; year:2024 ; extent:15
Advanced science ; (25.06.2024) (gesamt 15)
- Urheber
-
Chen, Deng
Zhao, Chunlong
Zhang, Jianqiu
Knol, Catharina W. J.
Osipyan, Angelina
Majerníková, Nad'a
Chen, Tingting
Xiao, Zhangping
Adriana, Jeaunice
Griffith, Andrew J.
Gamez, Abel Soto
van der Wouden, Petra E.
Coppes, Robert P.
Dolga, Amalia M.
Haisma, Hidde J.
Dekker, Frank J.
- DOI
-
10.1002/advs.202403963
- URN
-
urn:nbn:de:101:1-2406251421133.933757008611
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
14.08.2025, 10:53 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Chen, Deng
- Zhao, Chunlong
- Zhang, Jianqiu
- Knol, Catharina W. J.
- Osipyan, Angelina
- Majerníková, Nad'a
- Chen, Tingting
- Xiao, Zhangping
- Adriana, Jeaunice
- Griffith, Andrew J.
- Gamez, Abel Soto
- van der Wouden, Petra E.
- Coppes, Robert P.
- Dolga, Amalia M.
- Haisma, Hidde J.
- Dekker, Frank J.
Ähnliche Objekte (12)
Targeting cancer metabolism enhances radiosensitivity by impairing the heat shock response
mif
Mif'ičeskija vozzrěnija i mif'y Kitajcev
Recognizing emotions in bodies: Vagus nerve stimulation enhances recognition of anger while impairing sadness
Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke
SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair
Mif o Bakunine
Non-classical ferroptosis inhibition by a small molecule targeting PHB2
Glioblastoma mesenchymal subtype enhances antioxidant defence to reduce susceptibility to ferroptosis
Einrollenbandwaage MIF und DLE
Arijskij mif III Rejcha
Mechanisch integrierende Förderbandwaage (MIF)
Targeting cancer metabolism enhances radiosensitivity by impairing the heat shock response
mif
Mif'ičeskija vozzrěnija i mif'y Kitajcev
Recognizing emotions in bodies: Vagus nerve stimulation enhances recognition of anger while impairing sadness
Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke
SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair
Mif o Bakunine
Non-classical ferroptosis inhibition by a small molecule targeting PHB2
Glioblastoma mesenchymal subtype enhances antioxidant defence to reduce susceptibility to ferroptosis
Einrollenbandwaage MIF und DLE
Arijskij mif III Rejcha
Mechanisch integrierende Förderbandwaage (MIF)
Targeting cancer metabolism enhances radiosensitivity by impairing the heat shock response
mif
Mif'ičeskija vozzrěnija i mif'y Kitajcev
Recognizing emotions in bodies: Vagus nerve stimulation enhances recognition of anger while impairing sadness
Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke
SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair
Mif o Bakunine
Non-classical ferroptosis inhibition by a small molecule targeting PHB2
Glioblastoma mesenchymal subtype enhances antioxidant defence to reduce susceptibility to ferroptosis
Einrollenbandwaage MIF und DLE
Arijskij mif III Rejcha