Sun Liang, Yao Yizhou, Pan Guofeng, Zhan Shenghua, Shi Weiqiang, Lu Ting, Yuan Jinfeng, Tian Kangjun, Jiang Linhua, Song Shiduo, Zhu Xinguo, He Songbing
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Oncol Lett. 2018 Jul;16(1):594-602. doi: 10.3892/ol.2018.8648. Epub 2018 May 7.
Fatty acid synthase (FASN), the main enzyme involved in 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 . 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/Gli1) 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 . The silencing of FASN expression using siRNA reversed EMT at the protein and mRNA levels and decreased the expression of Gli1 via regulation of AMP-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/Gli1 signaling pathway, indicating that it may serve as a potential target for the treatment of GC.
脂肪酸合酶（FASN）是参与脂肪生成的主要酶，在多种肿瘤组织中过表达。此外，它与肿瘤细胞增殖、转移、上皮-间质转化（EMT）及预后不良相关。然而，FASN在胃癌（GC）细胞增殖、转移和EMT方面的确切功能及内在机制仍不清楚。本研究通过蛋白质印迹分析检测了18对随机选取的GC肿瘤组织及配对正常组织中FASN蛋白表达。随后将FASN特异性小干扰RNA（siRNA）转染至SGC-7901细胞，以检测FASN对细胞增殖和迁移的影响。采用蛋白质印迹法检测FASN、EMT相关标志物及雷帕霉素作用靶点/锌指蛋白GLI1（mTOR/Gli1）信号通路关键信号分子的蛋白表达。进行逆转录-定量聚合酶链反应检测FASN及EMT相关标志物的mRNA表达。与周围正常组织相比，GC组织中FASN水平更高。敲低FASN可抑制GC细胞增殖和转移。使用siRNA沉默FASN表达可在蛋白质和mRNA水平逆转EMT，并通过调节GC细胞中AMP活化蛋白激酶/mTOR和蛋白激酶B/mTOR信号降低Gli1的表达。抑制FASN通过靶向mTOR/Gli1信号通路抑制GC增殖和转移，表明其可能作为GC治疗的潜在靶点。
