SOAT1: A suitable target for therapy in high-grade astrocytic glioma? Journal Article
| Authors: | Löhr, M.; Härtig, W.; Schulze, A.; Kroiß, M.; Sbiera, S.; Lapa, C.; Mages, B.; Strobel, S.; Hundt, J. E.; Bohnert, S.; Kircher, S.; Janaki-Raman, S.; Monoranu, C. M. |
| Article Title: | 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | genetics; mutation; brain tumor; glioma; brain neoplasms; metabolism; adrenal cortex carcinoma; glioblastoma; targeted therapy; astrocytoma; mitotane; adrenocortical carcinoma; adrenal cortex tumor; adrenal cortex neoplasms; isocitrate dehydrogenase; idh1/2; lipid droplets; humans; human; soat1 |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 23 |
| Issue: | 7 |
| ISSN: | 1422-0067 |
| Publisher: | MDPI |
| Date Published: | 2022-04-01 |
| Start Page: | 3726 |
| Language: | English |
| DOI: | 10.3390/ijms23073726 |
| PUBMED: | 35409086 |
| PROVIDER: | scopus |
| PMCID: | PMC8998855 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
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