Inhibition of SOAT1 suppresses glioblastoma growth via blocking SREBP-1-mediated lipogenesis

摘要: Purpose: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing central role in lipid metabolism, is novel characteristic of glioblastoma (GBM). The aim this study was to identify effective approaches suppress GBM growth inhibition SREBP-1. As SREBP activation negatively endoplasmic reticulum (ER) cholesterol, we sought determine whether suppression O-acyltransferase (SOAT), key enzyme converting ER cholesterol esters (CE) store droplets (LDs), effectively suppressed SREBP-1 and blocked growth. Experimental Design: presence LDs glioma patient tumor tissues analyzed using immunofluorescence, immunohistochemistry, electronic microscopy. Western blotting real-time PCR were performed analyze protein levels gene expression cells, respectively. Intracranial xenografts used the effects genetically silencing SOAT1 on Results: Our unraveled that esterification LD formation are signature GBM, human patients with possess elevated correlate progression poor survival. We revealed highly expressed functions as player controlling storage GBM. Targeting suppresses prolongs survival xenograft models via SREBP-1–regulated synthesis. Conclusions: Cholesterol characteristics inhibiting block promising therapeutic strategy treat suppressing Clin Cancer Res; 22(21); 5337–48. ©2016 AACR.