Netrin-1 promotes gastric cancer cell proliferation and invasion via the receptor neogenin through PI3K/AKT signaling pathway
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Kai Yin1,2,*, Linjun Wang1,*, Xuan Zhang1,3,*, Zhongyuan He1,*, Yiwen Xia1, Jianghao Xu1, Song Wei1, Bowen Li1, Zheng Li1, Guangli Sun1, Qing Li1, Hao Xu1 and Zekuan Xu1,4
1Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
2Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
3Department of Hepatobiliary Surgery, Wuhu No.2 People 's Hospital, Wuhu, Anhui, China
4Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
*These authors contributed equally to this work
Zekuan Xu, email: firstname.lastname@example.org
Keywords: netrin-1, gastric cancer, neogenin, proliferation, invasion
Received: March 10, 2017 Accepted: April 27, 2017 Published: May 10, 2017
Netrin-1 is a laminin-related protein found to promote proliferation and invasion in multiple types of cancers. Recent studies have identified the function role of netrin-1 in several cancers; however, the influence of netrin-1 in human gastric cancer(GC) remains largely unknown. In this study, we found netrin-1 was upregulated in human GC tissues, where its expression correlated inversely with cancer stage and lymph node metastasis. We detected netrin-1 and its receptor knockdown significantly suppressed GC cells proliferation and invasion, while overexpression netrin-1 reversed these effects. Xenografted analyses using GC cells displayed significantly inhibition of tumor growth and metastasis by netrin-1 depletion. Furthermore, we identified that netrin-1 as a regulator of PI3K/AKT pathway to modulate GC cells proliferation and invasion abilities via its receptor neogenin. Taken together, our findings argued that netrin-1 and its receptor neogenin might act synergistically in promoting GC cells proliferation and invasion through the PI3K/AKT signaling pathway. It is conceivable that netrin-1 could be new therapeutic target to GC therapy.
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