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Open AccessArticle

Dinitrosopiperazine-Mediated Phosphorylated-Proteins Are Involved in Nasopharyngeal Carcinoma Metastasis

1
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China
2
Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China
3
Metallurgical Science and Engineering, Central South University, 21 Lushan South Road, Changsha 410083, China
4
Institute of Life and Health Engineering, National Engineering and Research Center for Genetic Medicine, Jinan University, 601 Huangpu Road West, Guangzhou 510632, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(11), 20054-20071; https://doi.org/10.3390/ijms151120054
Received: 22 July 2014 / Revised: 12 September 2014 / Accepted: 21 October 2014 / Published: 4 November 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
N,N'-dinitrosopiperazine (DNP) with organ specificity for nasopharyngeal epithelium, is involved in nasopharyngeal carcinoma (NPC) metastasis, though its mechanism is unclear. To reveal the pathogenesis of DNP-induced metastasis, immunoprecipitation was used to identify DNP-mediated phosphoproteins. DNP-mediated NPC cell line (6-10B) motility and invasion was confirmed. Twenty-six phosphoproteins were increased at least 1.5-fold following DNP exposure. Changes in the expression levels of selected phosphoproteins were verified by Western-blotting analysis. DNP treatment altered the phosphorylation of ezrin (threonine 567), vimentin (serine 55), stathmin (serine 25) and STAT3 (serine 727). Furthermore, it was shown that DNP-dependent metastasis is mediated in part through ezrin at threonine 567, as DNP-mediated metastasis was decreased when threonine 567 of ezrin was mutated. Strikingly, NPC metastatic tumors exhibited a higher expression of phosphorylated-ezrin at threonine 567 than the primary tumors. These findings provide novel insight into DNP-induced NPC metastasis and may contribute to a better understanding of the metastatic mechanisms of NPC tumors. View Full-Text
Keywords: dinitrosopiperazine; nasopharyngeal carcinoma; metastasis; protein phosphorylation; proteomics dinitrosopiperazine; nasopharyngeal carcinoma; metastasis; protein phosphorylation; proteomics
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Tan, G.; Tang, X.; Huang, D.; Li, Y.; Liu, N.; Peng, Z.; Zhang, Z.; Duan, C.; Lu, J.; Yan, G.; Tang, F. Dinitrosopiperazine-Mediated Phosphorylated-Proteins Are Involved in Nasopharyngeal Carcinoma Metastasis. Int. J. Mol. Sci. 2014, 15, 20054-20071.

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