Role of the ST6GAL1 sialyltransferase in regulating ovarian cancer cell metabolism.
ST6GAL1
cancer stem cells
hypoxia
metabolism
sialic acid
Journal
Glycobiology
ISSN: 1460-2423
Titre abrégé: Glycobiology
Pays: England
ID NLM: 9104124
Informations de publication
Date de publication:
06 10 2023
06 10 2023
Historique:
received:
21
03
2022
revised:
16
06
2023
accepted:
19
06
2023
pmc-release:
26
06
2024
medline:
23
10
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
The ST6GAL1 sialyltransferase, which adds α2-6-linked sialic acids to N-glycosylated proteins, is upregulated in many malignancies including ovarian cancer. Through its activity in sialylating select surface receptors, ST6GAL1 modulates intracellular signaling to regulate tumor cell phenotype. ST6GAL1 has previously been shown to act as a survival factor that protects cancer cells from cytotoxic stressors such as hypoxia. In the present study, we investigated a role for ST6GAL1 in tumor cell metabolism. ST6GAL1 was overexpressed (OE) in OV4 ovarian cancer cells, which have low endogenous ST6GAL1, or knocked-down (KD) in ID8 ovarian cancer cells, which have high endogenous ST6GAL1. OV4 and ID8 cells with modulated ST6GAL1 expression were grown under normoxic or hypoxic conditions, and metabolism was assessed using Seahorse technology. Results showed that cells with high ST6GAL1 expression maintained a higher rate of oxidative metabolism than control cells following treatment with the hypoxia mimetic, desferrioxamine (DFO). This enrichment was not due to an increase in mitochondrial number. Glycolytic metabolism was also increased in OV4 and ID8 cells with high ST6GAL1 expression, and these cells displayed greater activity of the glycolytic enzymes, hexokinase and phosphofructokinase. Metabolism maps were generated from the combined Seahorse data, which suggested that ST6GAL1 functions to enhance the overall metabolism of tumor cells. Finally, we determined that OV4 and ID8 cells with high ST6GAL1 expression were more invasive under conditions of hypoxia. Collectively, these results highlight the importance of sialylation in regulating the metabolic phenotype of ovarian cancer cells.
Identifiants
pubmed: 37364046
pii: 7207874
doi: 10.1093/glycob/cwad051
pmc: PMC10560082
doi:
Substances chimiques
Sialyltransferases
EC 2.4.99.-
Antineoplastic Agents
0
ST6GAL1 protein, human
EC 2.4.99.1
beta-D-Galactoside alpha 2-6-Sialyltransferase
EC 2.4.99.1
Antigens, CD
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
626-636Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008111
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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