title: Nrdp1-mediated ErbB3 degradation inhibits glioma cell migration and invasion by reducing cytoplasmic localization of p27(Kip1).
abstract: We previously reported that loss of Nrdp1 contributes to human glioma progression by reducing apoptosis. However, the role of Nrdp1 in glioma migration and invasion has not been investigated. Here, we report that ErbB3, a substrate of Nrdp1, is undetectable in normal brain tissues and grade II/III glioma tissues, but is abundant in a certain percentage of grade IV glioma tissues and is associated with the loss of Nrdp1. This suggests that Nrdp1 may be involved in glioma migration and invasion by regulating ErbB3. Thus, the role of Nrdp1/ErbB3 signaling in glioma cell migration and invasion was investigated using Nrdp1 loss- and gain-of-function. The results show that down-regulation of Nrdp1 by use of short hairpin RNA promoted glioma cell migration and invasion. In contrast, overexpression of Nrdp1 significantly inhibited glioma cell migration and invasion. Further investigation on molecular targets revealed that Nrdp1 decreased the level of ErbB3, which resulted in decreasing p-AKT thereby reducing cytoplasmic p27(Kip1). Taken together, these findings suggest that Nrdp1-mediated ErbB3 degradation suppresses glioma migration and invasion and that loss of Nrdp1 may amplify ErbB3 signaling to contribute to glioma migration and invasion. These findings suggest that Nrdp1 may be a target for glioma therapy.
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.|Neurosurgery Department of Jiangsu Haimen People's Hospital, Nantong, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Cao
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Shenshan
authors.initials: S
authors.lastname: Zou
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Bingxin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Hanmo
authors.initials: H
authors.lastname: Bao
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.|Neurosurgery Department of Jiangsu Xinyi People's Hospital, Xuzhou, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China. yu.rutong@163.com.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China. yu.rutong@163.com.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; C452580:RNF41 protein, human; D044767:Ubiquitin-Protein Ligases; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: ErbB3; Glioma; Nrdp1; PI3K; p27Kip1