Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma
Authors' conclusion
We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.
Study context
- Population
- Patients with ACC in two cohorts with survival and transcriptomic data; H295R adrenocortical cellstwo ACC cohorts
- Comparison
- SGPL1 expression
Methodological detailstwo ACC cohorts with survival and transcriptomic data, in vitro SGPL1-knockout and overexpressing H295R cells
- Two ACC cohorts with survival and transcriptomic data
- In vitro SGPL1-knockout and overexpressing H295R cells
Main finding
As reported in the abstract
- Increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1, correlated with reduced patient survival in both cohorts
- SGPL1 overexpression in H295R cells increased proliferation and migration and reduced apoptosis; SGPL1 knockout had the opposite effect
- RNA-seq: global increase in electron transport chain gene expression in overexpressing cells, correlating with increased aerobic respiration and glycolysis; opposite phenotype in cells lacking SGPL1
- Increased proliferation linked to metabolic substrate availability and increased capacity to use different fuel sources, particularly glucose, in overexpressing cells
Original publication
Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma. Eur J Endocrinol. Published 11 January 2023. doi:10.
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