1. Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma
- Author
-
Jack L Williams, Chris Smith, Charlotte Hall, Zakaa Khaled, Avinaash Maharaj, Ruth Kwong, James Pittaway, Josefina Casas, Laila Parvanta, Tarek Ezzat Abdel-Aziz, Fausto Palazzo, Teng-Teng Chung, Leonardo Guasti, Lou Metherell, and Rathi Prasad
- Subjects
Adrenocortical carcinoma ,Sphingolipids ,Endocrinology ,Endocrinology, Diabetes and Metabolism ,SGPL1 ,General Medicine ,Sphingosine-1-phosphate lyase - Abstract
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.
- Published
- 2023