Abstract
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.
Highlights
Gastric cancer is one of the most commonly diagnosed cancers, and it is a leading cause for cancer-related mortality, especially in Eastern Asia, Eastern Europe and South America [1, 2]
Since the expression levels of Enoyl coenzyme A hydratase short chain 1 (ECHS1) in the gastric cancer cell line increased as the degree of differentiation decreased, and the BGC-823 cells expressed the highest level of ECHS1 protein (Fig. 1A and B), we decided to use BGC-823 cells for further experiments in this study
We examined ECHS1 expression levels in gastric cancer cells and found that ECHS1 is highly expressed in these cell lines
Summary
Gastric cancer is one of the most commonly diagnosed cancers, and it is a leading cause for cancer-related mortality, especially in Eastern Asia, Eastern Europe and South America [1, 2]. Abnormalities in several signaling pathways are known to be involved in gastric cancers [4, 5]. It has been implicated in many cancers due to its essential role in cell proliferation regulation, cell cycle progression and cell survival [6,7,8]. Proteomic analysis and in vitro study reveal that the PI3K-PKB and STAT3 signaling pathways are functionally linked in cancer [21, 22]. These findings suggest that ECHS1 has a functional role in gastric cancer, which warrants more focused and detailed research on the functions of ECHS1 in human cancer. We explored the effect of ECHS1 attenuation on cell proliferation, cell migration and PKB and GSK3β protein activation
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