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Int. J. Mol. Sci. 2014, 15(11), 20054-20071;

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

Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China
Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China
Metallurgical Science and Engineering, Central South University, 21 Lushan South Road, Changsha 410083, China
Institute of Life and Health Engineering, National Engineering and Research Center for Genetic Medicine, Jinan University, 601 Huangpu Road West, Guangzhou 510632, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
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)
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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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