Zhu Xiao-San, Gao Peng, Dai Yi-Chen, Xie Jun-Pei, Zeng Wei, Lian Qing-Na
Department of Gastroenterology, Chenggong Hospital Affiliated to Xiamen University, Xiamen, Fujian, 361003, China,
Cell Mol Biol Lett. 2014 Dec;19(4):576-89. doi: 10.2478/s11658-014-0213-5. Epub 2014 Oct 23.
Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid β-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3β was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3β phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3β by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3β-related signaling pathways.
烯酰辅酶A水合酶短链1（ECHS1）是线粒体脂肪酸β氧化途径的重要组成部分。ECHS1表达改变与癌细胞增殖有关。本研究评估了ECHS1在人胃癌细胞系中的表达，并研究了ECHS1基因敲低对胃癌细胞增殖和迁移的影响。采用蛋白质印迹法分析人胃癌细胞系SGC-7901、BGC-823和MKN-28以及永生化人胃上皮黏膜GES-1细胞系中ECHS1蛋白水平。同时采用蛋白质印迹法检测ECHS1-RNA干扰的有效性。分别用CCK-8法和Transwell法检测siECHS1细胞的增殖和迁移情况。采用蛋白质印迹法评估PKB和GSK3β的磷酸化水平。低分化细胞中ECHS1蛋白水平显著高于高分化细胞和永生化胃上皮黏膜细胞。ECHS1 shRNA的稳定表达使siECHS1细胞的ECHS1蛋白水平降低了41%以上。siECHS1细胞中ECHS1基因的组成性敲低与细胞增殖和迁移的显著抑制有关。我们还观察到siECHS1细胞中PKB和GSK3β的磷酸化水平降低。人胃癌细胞中ECHS1表达增加。ECHS1表达增加通过诱导这两种激酶的磷酸化来激活PKB和GSK3β。ECHS1可能通过PKB和GSK3β相关信号通路在胃癌细胞增殖和迁移中发挥重要作用。
