SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Abstract

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.

• Authors: Mario Löhr, Wolfgang Härtig, Almut Schulze, Matthias Kroiß, Silviu Sbiera, Constantin Lapa, Bianca Mages, Sabrina Strobel, Jennifer Elisabeth Hundt, Simone Bohnert, Stefan Kircher, Sudha Janaki-Raman, Camelia-Maria Monoranu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 7 (Mar 28 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35409086 (Publication Type: Journal Article)

Chemical References

• Isocitrate Dehydrogenase
• Sterol O-Acyltransferase
• sterol O-acyltransferase 1

Topics

• Adrenal Cortex Neoplasms
• Adrenocortical Carcinoma
• Brain Neoplasms (metabolism)
• Glioblastoma (metabolism)
• Glioma (metabolism)
• Humans
• Isocitrate Dehydrogenase (genetics)
• Mutation
• Sterol O-Acyltransferase (metabolism)