Small interfering RNA-mediated knockdown of fatty acid synthase attenuates the proliferation and metastasis of human gastric cancer cells via the mTOR/Glil signaling pathway

Fatty acid synthase (FASN), the main enzyme involved in de novo lipogenesis, is overexpressed in several types of tumor tissues. In addition, it is associated with tumor cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) and a poor prognosis. However, the precise functions and internal mechanisms of FASN with regard to the proliferation, metastasis and EMT in gastric cancer (GC) cells remain elusive. The present study investigated FASN protein expression in 18 randomly selected pairs of GC tumors and matched normal tissues by western blot analysis. FASN-specific small interfering RNA (siRNA) was then transfected into SGC-7901 cells to examine the effect of FASN on proliferation and migration in vitro. Western blotting was used to detect the protein expression of FASN, EMT-related markers and key signaling molecules of the mechanistic target of rapamycin/zinc finger protein GLI1 (mTOR/Glil) pathway. Reverse transcription-quantitative polymerase chain reaction was conducted to detect the mRNA expression of FASN and EMT-related markers. The FASN level was higher in the GC tissues compared with that in the surrounding normal tissues. Knockdown of FASN suppressed GC cell proliferation and metastasis in vitro. The silencing of FASN expression using siRNA reversed EMT at the protein and mRNA levels and decreased the expression of Glil via regulation of AM[beta]-activated protein kinase/mTOR and protein kinase B/mTOR signaling in GC cells. Inhibition of FASN suppresses GC proliferation and metastasis through targeting of the mTOR/Glil signaling pathway, indicating that it may serve as a potential target for the treatment of GC.