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UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells
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UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells
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Journal Article
UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells
2020
Overview
The only enzyme in the
glycosphingolipid
(GSL) metabolic pathway, which produces
glucosylceramide
(GlcCer)
de novo
is
UDP-glucose ceramide glucosyltransferase
(UGCG). UGCG is linked to pro-cancerous processes such as multidrug resistance development and increased proliferation in several cancer types. Previously, we showed an UGCG-dependent glutamine metabolism adaption to nutrient-poor environment of breast cancer cells. This adaption includes reinforced oxidative stress response and fueling the
tricarboxylic acid
(TCA) cycle by increased glutamine oxidation. In the current study, we investigated glycolytic and oxidative metabolic phenotypes following UGCG
overexpression
(OE). UGCG overexpressing MCF-7 cells underwent a metabolic shift from quiescent/aerobic to energetic metabolism by increasing both glycolysis and oxidative glucose metabolism. The energetic metabolic phenotype was not associated with increased mitochondrial mass, however, markers of mitochondrial turnover were increased. UGCG OE altered sphingolipid composition of the
endoplasmic reticulum
(ER)/mitochondria fractions that may contribute to increased mitochondrial turnover and increased cell metabolism. Our data indicate that GSL are closely connected to cell energy metabolism and this finding might contribute to development of novel therapeutic strategies for cancer treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group
