title: 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.
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasumoto
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Linda Koshy
authors.initials: LK
authors.lastname: Vaidyan
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Majid
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ogata
authors.affiliation: Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sadahiro
authors.affiliation: Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002569:Cerulenin / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D002569:Cerulenin; D064429:Fatty Acid Synthases