title: NEDD4-1 regulates migration and invasion of glioma cells through CNrasGEF ubiquitination in vitro.
abstract: Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) plays a great role in tumor cell growth, but its function and mechanism in cell invasive behavior are totally unknown. Here we report that NEDD4-1 regulates migration and invasion of malignant glioma cells via triggering ubiquitination of cyclic nucleotide Ras guanine nucleotide exchange factor (CNrasGEF) using cultured glioma cells. NEDD4-1 overexpression promoted cell migration and invasion, while its downregulation specifically inhibited them. However, NEDD4-1 did not affect the proliferation and apoptosis of glioma cells. NEDD4-1 physically interacted with CNrasGEF and promoted its poly-ubiquitination and degradation. Contrary to the effect of NEDD4-1, CNrasGEF downregulation promoted cell migration and invasion, while its overexpression inhibited them. Importantly, downregulation of CNrasGEF facilitated the effect of NEDD4-1-induced cell migration and invasion. Interestingly, aberrant up-regulated NEDD4-1 showed reverse correlation with CNrasGEF protein level but not with its mRNA level in glioma tissues. Combined with the in vitro results, the result of glioma tissues indicated post-translationally modification effect of NEDD4-1 on CNrasGEF. Our study suggests that NEDD4-1 regulates cell migration and invasion through ubiquitination of CNrasGEF in vitro.
authors: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China ; The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Hao
authors: H
authors: Zhang
authors: Wenchen
authors: W
authors: Nie
authors: Xu
authors: X
authors: Zhang
authors: Gentang
authors: G
authors: Zhang
authors: Zhiqiang
authors: Z
authors: Li
authors: Huaibing
authors: H
authors: Wu
authors: Qiong
authors: Q
authors: Shi
authors: Yong
authors: Y
authors: Chen
authors: Zhijun
authors: Z
authors: Ding
authors: Xiuping
authors: X
authors: Zhou
authors: Rutong
authors: R
authors: Yu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000075702:Nedd4 Ubiquitin Protein Ligases; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D020662:Guanine Nucleotide Exchange Factors; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C403525:RAPGEF2 protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases