title: Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro.
abstract: FASN plays an important role in the malignant phenotype of various tumors. Our previous studies show that inhibition FASN could induce apoptosis and inhibit proliferation in human osteosarcoma (OS) cell in vivo and vitro. The aim in this study was to investigate the effect of inhibition FASN on the activity of HER2/PI3K/AKT axis and invasion and migration of OS cell. The expression of FASN, HER2 and p-HER2(Y1248) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between FASN and p-HER2 as well as HER2 was investigated. The results showed that there was a positive correlation between FASN and HER2 as well as p-HER2 protein expression. The U-2 OS cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid. FASN mRNA was measured by RT-PCR. Western blot assays was performed to examine the protein expression of FASN, HER2, p-HER2(Y1248), PI3K, Akt and p-Akt (Ser473). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. The results showed that the activity of HER2/PI3K/AKT signaling pathway was suppressed by inhibiting FASN. Meanwhile, the U-2OS cells migration and invasion were also impaired by inhibiting the activity of FASN/HER2/PI3K/AKT. Our results indicated that inhibition of FASN suppresses OS cell invasion and migration via down-regulation of the "HER2/PI3K/AKT" axis in vitro. FASN blocker may be a new therapeutic strategy in OS management.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Jiangxi, PR China.
authors.forename: Tao Fang
authors.initials: TF
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Ai Fen
authors.initials: AF
authors.lastname: Peng
authors.forename: Qing Feng
authors.initials: QF
authors.lastname: Luo
authors.forename: Zhi Li
authors.initials: ZL
authors.lastname: Liu
authors.forename: Rong Ping
authors.initials: RP
authors.lastname: Zhou
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wen Zhao
authors.initials: WZ
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D012516:Osteosarcoma / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D064429:Fatty Acid Synthases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: Fatty acid synthase (FASN); HER2/PI3K/AKT signaling pathway; Invasion; Migration; Osteosarcoma (OS)