| Identifikační kód |
RIV/00216208:11160/20:10426078 |
| Název v anglickém jazyce |
Impact of 17 beta-HSD12, the 3-ketoacyl-CoA reductase of long-chain fatty acid synthesis, on breast cancer cell proliferation and migration |
| Druh |
J - Recenzovaný odborný článek (Jimp, Jsc a Jost) |
| Poddruh |
J/A - Článek v odborném periodiku je obsažen v databázi Web of Science společností Thomson Reuters s příznakem „Article“, „Review“ nebo „Letter“ (Jimp) |
| Jazyk |
eng - angličtina |
| Vědní obor |
30104 - Pharmacology and pharmacy |
| Rok uplatnění |
2020 |
| Kód důvěrnosti údajů |
S - Úplné a pravdivé údaje o výsledku nepodléhající ochraně podle zvláštních právních předpisů. |
| Počet výskytů výsledku |
1 |
| Popis výsledku v anglickém jazyce |
Metabolic reprogramming of tumor cells involves upregulation of fatty acid (FA) synthesis to support high bioenergetic demands and membrane synthesis. This has been shown for cytosolic synthesis of FAs with up to 16 carbon atoms. Synthesis of long-chain fatty acids (LCFAs), including omega-6 and omega-3 polyunsaturated FAs, takes place at the endoplasmic reticulum. Despite increasing evidence for an important role of LCFAs in cancer, the impact of their synthesis in cancer cell growth has scarcely been studied. Here, we demonstrated that silencing of 17 beta-hydroxysteroid dehydrogenase type 12 (17 beta-HSD12), essentially catalyzing the 3-ketoacyl-CoA reduction step in LCFA production, modulates proliferation and migration of breast cancer cells in a cell line-dependent manner. Increased proliferation and migration after 17 beta-HSD12 knockdown were partly mediated by metabolism of arachidonic acid towards COX2 and CYP1B1-derived eicosanoids. Decreased proliferation was rescued by increased glucose concentration and was preceded by reduced ATP production through oxidative phosphorylation and spare respiratory capacity. In addition, 17 beta-HSD12 silencing was accompanied by alterations in unfolded protein response, including a decrease in CHOP expression and increase in eIF2 alpha activation and the folding chaperone ERp44. Our study highlights the significance of LCFA biosynthesis for tumor cell physiology and unveils unknown aspects of breast cancer cell heterogeneity. |
| Klíčová slova oddělená středníkem |
Endoplasmic reticulum;Unfolded protein response;Long-chain fatty acid;17 beta-Hydroxysteroid dehydrogenase;Cancer;Biosynthesis |
| Stránka www, na které se nachází výsledek |
https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=hEvW2uHoUZ |
| DOI výsledku |
10.1007/s00018-019-03227-w |
| Odkaz na údaje z výzkumu |
- |