Downregulation of fatty acid synthase complex suppresses cell migration by targeting phosphor-AKT in bladder cancer

Mol Med Rep. 2016 Feb;13(2):1845-50. doi: 10.3892/mmr.2015.4746. Epub 2015 Dec 30.

Abstract

The aim of the present study was to investigate the effect of fatty acid synthase complex (FASN) on the migration capacity of bladder transitional cell carcinoma (BTCC) cells and the involvement of matrix metalloproteinase‑9 (MMP‑9) via targeting of phospho‑AKT (p‑AKT). FASN‑specific small‑interfering RNA (FASN‑siRNA) was used to inhibit FASN gene expression in the 5637 and 253J BTCC cell lines. The knockdown efficiency of FAM‑conjugated FASN‑siRNA was confirmed by fluorescence microscopy. The migratory abilities of BTCC cells were assessed using a Transwell assay. Furthermore, protein and mRNA expression of FASN, p‑AKT, AKT, and migration‑associated protein MMP‑9 were detected by western blot analysis. Treatment with FASN inhibitor Cer and FASN‑siRNA decreased the migratory capacity of bladder cancer cells and reduced the levels of p‑AKT as well as the expression of MMP‑9. These results indicated that FASN inhibition suppressed the migratory capacity of BTCC cells through suppressing AKT activation and consequently reducing MMP‑9 expression. Targeting FASN may represent a promising novel therapeutic strategy for BTCC.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cerulenin / pharmacology
  • Down-Regulation* / drug effects
  • Fatty Acid Synthases / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / metabolism
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • RNA, Small Interfering
  • Cerulenin
  • Fatty Acid Synthases
  • Proto-Oncogene Proteins c-akt