Adenine nucleotide translocase 2 silencing promotes metabolic reprogramming in P19 embryonal carcinoma stem cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00637880" target="_blank" >RIV/86652036:_____/25:00637880 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10510890

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0925443925002509?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0925443925002509?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbadis.2025.167902" target="_blank" >10.1016/j.bbadis.2025.167902</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Adenine nucleotide translocase 2 silencing promotes metabolic reprogramming in P19 embryonal carcinoma stem cells

Popis výsledku v původním jazyce

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 CSCdriven tumor progression.

Název v anglickém jazyce

Adenine nucleotide translocase 2 silencing promotes metabolic reprogramming in P19 embryonal carcinoma stem cells

Popis výsledku anglicky

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 CSCdriven tumor progression.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

<a href="/cs/project/GA22-07091S" target="_blank" >GA22-07091S: SUCLG2 jako nový tumor supresor působící na mitochondriální metabolismus: Molekulární mechanismus a klinická relevance</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biochimica Et Biophysica Acta-Molecular Basis of Disease

ISSN

0925-4439

e-ISSN

1879-260X

Svazek periodika

1871

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

167902

Kód UT WoS článku

001498123100001

EID výsledku v databázi Scopus

2-s2.0-105005251263