Role of the sodium/calcium exchanger type 3 in cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F25%3A00143828" target="_blank" >RIV/00216224:14110/25:00143828 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0171933525000184?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0171933525000184?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejcb.2025.151493" target="_blank" >10.1016/j.ejcb.2025.151493</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of the sodium/calcium exchanger type 3 in cancer cells

Popis výsledku v původním jazyce

The sodium/calcium exchanger (NCX) type 1 has been well described in various cancers, but little is known about the other two NCX types (NCX2 and NCX3). In this study, we used the selective blocker of NCX3 - YM244769 to investigate changes in apoptosis induction, migration, proliferation, intracellular calcium and ATP in four cancer cell lines - DLD1, HeLa, MDA-MB-231 and JIMT1. In all four cell lines we observed a concentration-dependent increase in the number of apoptotic cells, as well as reduced migration and proliferation. Induction of hypoxic conditions did not alter the response of these cells to YM-244769 in any of the abovementioned parameters. These results indicate the role of NCX3 in cancer cell migration, proliferation and apoptosis, as inhibition of NCX1 by the specific blocker SEA0400 had no significant effect on these parameters. However, we verified the effect of NCX3 inhibition by using CRISPR/Cas9 to generate clones in which the SLC8A3 (NCX3) gene was deleted, and we obtained the same results. In addition, mitochondrial respiration was impaired in the clones with NCX3 knocked-out, suggesting that NCX3 also play a role in bioenergetics. In conclusion, we have clearly shown that NCX3 plays an important anti-apoptotic, pro-migratory and proliferative role in the cancer cells by affecting mitochondrial bioenergetics, thus supporting their survival and fate.

Název v anglickém jazyce

Role of the sodium/calcium exchanger type 3 in cancer cells

Popis výsledku anglicky

The sodium/calcium exchanger (NCX) type 1 has been well described in various cancers, but little is known about the other two NCX types (NCX2 and NCX3). In this study, we used the selective blocker of NCX3 - YM244769 to investigate changes in apoptosis induction, migration, proliferation, intracellular calcium and ATP in four cancer cell lines - DLD1, HeLa, MDA-MB-231 and JIMT1. In all four cell lines we observed a concentration-dependent increase in the number of apoptotic cells, as well as reduced migration and proliferation. Induction of hypoxic conditions did not alter the response of these cells to YM-244769 in any of the abovementioned parameters. These results indicate the role of NCX3 in cancer cell migration, proliferation and apoptosis, as inhibition of NCX1 by the specific blocker SEA0400 had no significant effect on these parameters. However, we verified the effect of NCX3 inhibition by using CRISPR/Cas9 to generate clones in which the SLC8A3 (NCX3) gene was deleted, and we obtained the same results. In addition, mitochondrial respiration was impaired in the clones with NCX3 knocked-out, suggesting that NCX3 also play a role in bioenergetics. In conclusion, we have clearly shown that NCX3 plays an important anti-apoptotic, pro-migratory and proliferative role in the cancer cells by affecting mitochondrial bioenergetics, thus supporting their survival and fate.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

—

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

European Journal of Cell Biology

ISSN

0171-9335

e-ISSN

1618-1298

Svazek periodika

104

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

1-11

Kód UT WoS článku

001488075200001

EID výsledku v databázi Scopus

2-s2.0-105004026192