title: Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma.
abstract: As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion. We hypothesize that proN-cadherin might cause homotypic adhesion loss within neighboring cells and at the same time promote heterotypic adhesion within the extracellular matrix (ECM) through a certain mechanism. This study also demonstrates that the interaction between GDNF and proN-cadherin activates specific intracellular signaling pathways; furthermore, GDNF promoted the secretion of matrix metalloproteinase-9 (MMP-9), which degrades the ECM via proN-cadherin. To reach the future goal of developing novel therapies of glioma, this study, reveals a unique mechanism of glioma cell migration and invasion.
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Baole
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Yao
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Food and Environmental, Dalian University of Technology, Panjin Campus, Panjin 124221, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
authors.forename: Dian Shuai
authors.initials: DS
authors.lastname: Gao
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D014162:Transfection
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D011498:Protein Precursors; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: GDNF; glioma cells; invasion; migration; precursor N-cadherin