Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells

Abstract

Cellular metabolic changes, especially to lipid metabolism, have recently been recognized as a hallmark of various cancer cells. However, little is known about the significance of cellular lipid metabolism in the regulation of biological activity of glioma stem cells (GSCs). In this study, we examined the expression and role of fatty acid synthase (FASN), a key lipogenic enzyme, in GSCs. In the de novo lipid synthesis assay, GSCs exhibited higher lipogenesis than differentiated non-GSCs. Western blot and immunocytochemical analyses revealed that FASN is strongly expressed in multiple lines of patient-derived GSCs (G144 and Y10), but its expression was markedly reduced upon differentiation. When GSCs were treated with 20 μM cerulenin, a pharmacological inhibitor of FASN, their proliferation and migration were significantly suppressed and de novo lipogenesis decreased. Furthermore, following cerulenin treatment, expression of the GSC markers nestin, Sox2 and fatty acid binding protein (FABP7), markers of GCSs, decreased while that of glial fibrillary acidic protein (GFAP) expression increased. Taken together, our results indicate that FASN plays a pivotal role in the maintenance of GSC stemness, and FASN-mediated de novo lipid biosynthesis is closely associated with tumor growth and invasion in glioblastoma.

Prognostic power of a lipid metabolism gene panel for diffuse gliomas

“…24,25 Expression of fatty acid synthase (FASN) increased with tumour grade, and pharmacological inhibition of FASN significantly decreased the proliferation and migration of glioma stem cells. 26,27 In this study, we profiled the lipid metabolism phenotype between low-grade glioma and GBM with gene expression data. The results found GBM exhibited enrichment of glycosphingolipid metabolic progress, whereas LGG displayed enrichment of phosphatidylinositol metabolic progress, which offered new implications regarding glioma lipid metabolism status and targeted therapy.…”

BNIP3 induction by hypoxia stimulates FASN-dependent free fatty acid production enhancing therapeutic potential of umbilical cord blood-derived human mesenchymal stem cells

“…For example, FASN-dependent lipogenesis is highly active in adult neural stem and progenitor cells that are associated with adult neurogenesis [56]. FASN inhibition by cerulenin suppressed proliferation and migration as well as stemness marker expression in glioma stem cell [57]. In addition, SCD1 has a tumor suppressive role in survival of leukemia stem cells and eliminates undifferentiated tumorigenic pluripotent stem cells [58], [59].…”

NADPH accumulation is responsible for apoptosis in breast cancer cells induced by fatty acid synthase inhibition

“…Unlike normal tissue cells, cancer cells have active de novo lipogenesis [26]. As a key enzyme involved in lipogensis, FAS is highly expressed in many cancers including breast cancers and is supposed to support cell proliferation [27].…”