J Cancer 2019; 10(14):3197-3207. doi:10.7150/jca.30230 This issue

Research Paper

Netrin-1 promotes cell neural invasion in gastric cancer via its receptor neogenin

Kai Yin1,2*, Linjun Wang2*, Yiwen Xia2*, Shengchun Dang1, Xuan Zhang3, Zhongyuan He2, Jianghao Xu2, Mengyuan Shang4, Zekuan Xu2✉

1. Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
2. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
3. Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
4. Department of Ultrasound Diagnosis, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Yin K, Wang L, Xia Y, Dang S, Zhang X, He Z, Xu J, Shang M, Xu Z. Netrin-1 promotes cell neural invasion in gastric cancer via its receptor neogenin. J Cancer 2019; 10(14):3197-3207. doi:10.7150/jca.30230. Available from https://www.jcancer.org/v10p3197.htm

File import instruction


Neural invasion (NI) is one of the important routes for local spread of gastric cancer (GC) correlated with poor prognosis. However, the exact cellular characteristics and molecular mechanisms of NI in GC are still unclear. Netrin-1(NTN1) as an axon guidance molecule was firstly found during neural system development. Importantly, NTN1 has an essential role in the progression of malignant tumor and specifically mediates the induction of invasion. In this study, we found NTN1 expression was significantly increased in 97 tumor tissues from GC patients and positively correlated with NI (p<0.05). In addition, we detected NTN1 knockdown significantly suppressed GC cells migration and invasion. Moreover, our results showed that reciprocity was observed between GC cells and neurites colonies in dorsal root ganglia (DRG)-GC cells co-culture vitro model. GC cells with NTN1 silencing could suppress their abilities to navigate along surrounding neuritis and this effect was depended on its receptor neogenin. In vivo, NTN1 inhibition also decreased GC cells sciatic nerve invasion. Taken together, our findings argue that NTN1 and its receptor neogenin might act synergistically in promoting GC cells neural invasion. Inhibiting the activity of NTN1 could be a potential strategy targeting NI in GC therapy.

Keywords: Netrin-1, Gastric cancer, Neural invasion, Neogenin