NEDD4-1 Regulates Migration and Invasion of Glioma Cells through CNrasGEF Ubiquitination In VitroReport as inadecuate




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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.



Author: Hao Zhang , Wenchen Nie , Xu Zhang, Gentang Zhang, Zhiqiang Li, Huaibing Wu, Qiong Shi, Yong Chen, Zhijun Ding, Xiuping Zhou , Ru

Source: http://plos.srce.hr/



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