Adenine nucleotide translocase 2 silencing promotes metabolic reprogramming in P19 embryonal carcinoma stem cells
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
40381816
DOI
10.1016/j.bbadis.2025.167902
PII: S0925-4439(25)00250-9
Knihovny.cz E-zdroje
- Klíčová slova
- ANT2, Hexokinase II, Metabolism, Mitochondria, Spheroids, cancer stem cells,
- MeSH
- buněčná diferenciace MeSH
- glykolýza MeSH
- hexokinasa metabolismus genetika MeSH
- kmenové buňky embryonálního karcinomu * metabolismus patologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií MeSH
- metabolické přeprogramování MeSH
- mitochondrie metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky * metabolismus patologie MeSH
- oxidativní fosforylace MeSH
- proliferace buněk MeSH
- translokátor adeninových nukleotidů 2 * genetika metabolismus MeSH
- umlčování genů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- hexokinasa MeSH
- translokátor adeninových nukleotidů 2 * MeSH
Although controversial, cancer stem cells (CSCs) are thought to be one tumor component, being characterized by their strong self-renewal and survival properties. Cancer cells, CSCs included, are thought to rely mostly on glycolysis, even in the presence of oxygen, which confers them adaptive advantages. Adenine nucleotide translocator 2 (ANT2), responsible for the exchange of ADP and ATP in the mitochondrial inner membrane, has been correlated with a higher glycolytic metabolism and is known to be overexpressed in cancer cells. Using P19 embryonal carcinoma stem cells, we inhibited ANT2 translation by using siRNA. ANT2 protein levels were shown to be overexpressed in P19 undifferentiated cells (P19SCs) when compared to their differentiated counterparts (P19dCs). Furthermore, we showed here that the OXPHOS machinery and mitochondrial membrane potential are compromised after ANT2 depletion, leading to a metabolic adaptation towards a less oxidative phenotype. Interestingly, hexokinase II levels were downregulated, which was also accompanied by decreased cell growth, and reduced ability to form spheroids. Our findings underscore ANT2 as a key regulator of metabolic remodeling and cell survival of cancer stem-like cells, suggesting its potential as a therapeutic target for controlling CSC-driven tumor progression.
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