Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells
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Wenjie Qin1,2,*, Chao Li1,2,*, Wen Zheng1,2,*, Qingqu Guo1,2, Yuefeng Zhang1,2, Muxing Kang1,2, Bo Zhang1,2, Bin Yang1,2, Baozhong Li3, Haijun Yang4, Yulian Wu1,2
1Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
2Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China
3Department of Oncosurgery, Anyang Tumor Hospital, Henan, P. R. China
4Department of Pathology, Anyang Tumor Hospital, Henan, P. R. China
*These authors have contributed equally to this work
Yulian Wu, e-mail: firstname.lastname@example.org
Keywords: autophagy inhibition, metastasis, glycolysis, reactive oxygen species (ROS), antioxidant
Received: April 28, 2015 Accepted: October 02, 2015 Published: October 14, 2015
Autophagy defect has been shown to be correlated with malignant phenotype and poor prognosis of human cancers, however, the detailed mechanisms remain obscure. In this study, we investigated the biological changes induced by autophagy inhibition in gastric cancer. We showed that inhibition of autophagy in gastric cancer cells promotes epithelial-mesenchymal transition (EMT) and metastasis, alters metabolic phenotype from mitochondrial oxidative phosphorylation to aerobic glycolysis and converts cell phenotype toward malignant, which maybe further contribute to chemoresistance and poor prognosis of gastric cancer. We also identified that the EMT and metabolism alterations induced by autophagy inhibition were dependent on ROS-NF-κB-HIF-1α pathway. More importantly, scavenging of ROS by the antioxidant N-acetylcysteine (NAC) attenuated activation of NF-κB and HIF-1α in autophagy-deficient gastric cancer cells, and autophagy inhibition induced metastasis and glycolysis were also diminished by NAC in vivo. Taken together, our findings suggested that autophagy defect promotes metastasis and glycolysis of gastric cancer, and antioxidants could be used to improve disease outcome for gastric cancer patients with autophagy defect.
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