TY  - JOUR
A1  - Löhr, Mario
A1  - Härtig, Wolfgang
A1  - Schulze, Almut
A1  - Kroiß, Matthias
A1  - Sbiera, Silviu
A1  - Lapa, Constantin
A1  - Mages, Bianca
A1  - Strobel, Sabrina
A1  - Hundt, Jennifer Elisabeth
A1  - Bohnert, Simone
A1  - Kircher, Stefan
A1  - Janaki-Raman, Sudha
A1  - Monoranu, Camelia-Maria
T1  - SOAT1: A suitable target for therapy in high-grade astrocytic glioma?
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - SOAT1
KW  - glioblastoma
KW  - astrocytoma
KW  - IDH1/2
KW  - lipid droplets
KW  - mitotane
KW  - targeted therapy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284178
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -