Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma

Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC.
This work was supported by Barts Charity grants MGU0361 to L.M. and R.P.; MGU0438 to L.M.; MGU0528 to R.K.; MGU0436 to L.G.; Government of Trinidad and Tobago Research Fellowship to A.M.; Medical Research Council (MRC) UK Clinical Academic Research Partner grant (MR/T02402X/1) to R.P. and MRC clinical research fellowships (MR/S022155/1) to J.P. and (MR/W015935/1) to R.K.