Inhibition of fatty acid synthase decreases expression of stemness markers in glioma stem cells

Yuki Yasumoto, Hirofumi Miyazaki, Linda Koshy Vaidyan, Yoshiteru Kagawa, Majid Ebrahimi, Yui Yamamoto, Masaki Ogata, Yu Katsuyama, Hirokazu Sadahiro, Michiyasu Suzuki, Yuji Owada

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49 Citations (Scopus)

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 uM 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.

Original languageEnglish
Article numbere0147717
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yasumoto, Y., Miyazaki, H., Vaidyan, L. K., Kagawa, Y., Ebrahimi, M., Yamamoto, Y., Ogata, M., Katsuyama, Y., Sadahiro, H., Suzuki, M., & Owada, Y. (2016). Inhibition of fatty acid synthase decreases expression of stemness markers in glioma stem cells. PloS one, 11(1), [e0147717]. https://doi.org/10.1371/journal.pone.0147717