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Silencing of AQP3 induces apoptosis of gastric cancer cells via downregulation of glycerol intake and downstream inhibition of lipogenesis and autophagy

Authors Chen L, Li Z, Zhang Q, Wei S, Li B, Zhang X, Zhang L, Li Q, Xu H, Xu Z

Received 6 February 2017

Accepted for publication 5 May 2017

Published 1 June 2017 Volume 2017:10 Pages 2791—2804

DOI https://doi.org/10.2147/OTT.S134016

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai

Liang Chen,* Zheng Li,* Qiang Zhang,* Song Wei, Bowen Li, Xuan Zhang, Lei Zhang, Qing Li, Hao Xu, Zekuan Xu

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Abstract: Gastric cancer (GC) has a poor prognosis and is a leading cause of cancer-related death. Optimal therapeutic targets have not been identified. AQP3 is capable of transporting glycerol across the cytomembrane. Previous studies have shown that AQP3 is involved in proliferation, invasion and migration by regulating glycerol and lipid metabolism in diverse cancer cell types. However, the potential roles of glycerol and lipid metabolism in AQP3-related cell apoptosis in GC remain unclear. In this study, we observed that AQP3 expression was upregulated in tumor tissues, and positively correlated with tumor size, lymph node metastasis and glycerol concentration in human GC samples. Silencing of AQP3 resulted in decreased glycerol intake and impaired lipid synthesis, which contributed to increased cell apoptosis. Furthermore, inhibition of autophagy induced by AQP3 knockdown promoted cell apoptosis. Administration of either glycerol or rapamycin restored cell viability, and overexpression of AQP3 increased cell viability by upregulating cellular glycerol metabolism and autophagy. Our study demonstrates that the increase in cell apoptosis of AQP3-deficient GC cells is a consequence of reduced glycerol uptake and lipogenesis and is associated with autophagy inhibition induced by AQP3 deficiency.

Keywords: AQP3, glycerol uptake, lipid metabolism, autophagy, apoptosis

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