Downregulation of HADH promotes gastric cancer progression via Akt signaling pathway

HADH is a key enzyme in fatty acid oxidation. The aim of this study was to identify the role of HADH in gastric cancer. We analyzed the expression of HADH in 102 pairs of gastric cancer samples. Western blot analysis revealed that HADH was decreased in stage I/II gastric cancer samples compared to matched adjacent normal gastric tissue, and its expression was further decreased in stage III/IV samples. Importantly, the reduced expression of HADH was associated with increased expression of p-Akt and reduced expression of PTEN in the gastric carcinoma tumor samples. To determine the significance of HADH downregulation in gastric cancer progression, we tested the impact of HADH knockdown or overexpression on the migration and invasion of the gastric cancer cells using a transwell assay. Knockdown of HADH significantly promoted gastric cancer cell migration and invasion, which was associated with increased expression of p-Akt. The PI3K inhibitor LY294002 inhibited HADH shRNA induced migration/invasion, and abolished the upregulation of p-Akt. By contrast, HADH overexpression inhibited the migration and invasion of MKN45 cells. Herein, for the first time, we demonstrate that downregulation of HADH promotes gastric cancer progression via activation of Akt signaling pathway.