Neurturin promotes tumor cell motility and angiogenesis in colorectal cancer

Shuyun Wang; Limin Nie; Yuxiao Song; Fang Zhang; Xiaozheng Chen; Wenjing Shi; Zijiang Yang; Yuping Sun; Qi Dang; Aiqin Gao

doi:10.1016/j.yexcr.2022.113049

Neurturin promotes tumor cell motility and angiogenesis in colorectal cancer

Exp Cell Res. 2022 Apr 1;413(1):113049. doi: 10.1016/j.yexcr.2022.113049. Epub 2022 Jan 31.

Authors

Shuyun Wang¹, Limin Nie², Yuxiao Song³, Fang Zhang⁴, Xiaozheng Chen⁵, Wenjing Shi⁴, Zijiang Yang⁴, Yuping Sun⁶, Qi Dang⁷, Aiqin Gao⁸

Affiliations

¹ Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China; Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
² Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China; Department of Oncology, Caoxian People's Hospital, Heze, Shandong, PR China.
³ Jinan Center for Disease Control and Prevention, Jinan, Shandong, PR China.
⁴ Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
⁵ Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
⁶ Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
⁷ Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, PR China. Electronic address: dangqi123456@126.com.
⁸ Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, PR China. Electronic address: 13954196383@163.com.

PMID: 35114191
DOI: 10.1016/j.yexcr.2022.113049

Abstract

Neurturin (NRTN) is one of the glial cell line-derived neurotrophic factor family ligands crucial for neuron growth, differentiation and maintenance. Recent studies showed NRTN promotes an aggressive pancreatic cancer phenotype, and predicts shorter survival in lung cancer patients. However, its expression and function in colorectal cancer (CRC) remain unclear. Herein, we found NRTN was enriched in CRC cells, and predicted poor patients outcomes. Upregulated NRTN enhanced the migration and invasion of CRC cells and vascularization of endothelial cells. In mechanism, NRTN promoted ZEB1/N-cadherin and vascular endothelial growth factor (VEGF)-A expression in CRC cells, which were responsible for tumor cell motility and angiogenesis, respectively. More importantly, NRTN inhibition prevented CRC metastasis and angiogenesis in vivo. In conclusion, NRTN promotes CRC cells motility and tumor angiogenesis via inducing ZEB1/N-cadherin and VEGF-A overexpression. It is a potential therapeutic target and negative prognostic biomarker for CRC patients.

Keywords: Angiogenesis; Colorectal cancer; Invasion; Metastasis; Migration; Neurturin.