Research Papers:
Downregulation of HADH promotes gastric cancer progression via Akt signaling pathway
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Abstract
Congcong Shen1,*, Yao-Hua Song1,*, Yufeng Xie2,*, Xiaoxiao Wang1,*, Yunliang Wang3,*, Chao Wang4,*, Songbai Liu5, Sheng-Li Xue6, Yangxin Li7, Bin Liu8, Zaixiang Tang9, Weichang Chen4, Jenny Song1, Hesham M. Amin10 and Jin Zhou3
1Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, P. R. China
2Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
3Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
4Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
5Suzhou Vocational Health College, Suzhou Key Laboratory of Biotechnology for Laboratory Medicine, Suzhou, P. R. China
6Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, P. R. China
7Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, P. R. China
8Department of Cardiology, Second Hospital of Jilin University, Changchun, P. R. China
9Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, P. R. China
10Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
*These authors have contributed equally to this work
Correspondence to:
Yao-Hua Song, email: [email protected]
Jin Zhou, email: [email protected]
Keywords: gastric cancer, HADH, fatty acids, migration, invasion
Received: January 21, 2017 Accepted: June 30, 2017 Published: July 18, 2017
ABSTRACT
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.
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