Tan Gongjun, Tang Xiaowei, Huang Damao, Li Yuejin, Liu Na, Peng Zhengke, Zhang Zhenlin, Duan Chaojun, Lu Jinping, Yan Guangrong, Tang Faqing
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China.
Metallurgical Science and Engineering, Central South University, 21 Lushan South Road, Changsha 410083, China.
Int J Mol Sci. 2014 Nov 4;15(11):20054-71. doi: 10.3390/ijms151120054.
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.
N,N'-二亚硝基哌嗪（DNP）对鼻咽上皮具有器官特异性，参与鼻咽癌（NPC）转移，但其机制尚不清楚。为揭示DNP诱导转移的发病机制，采用免疫沉淀法鉴定DNP介导的磷酸化蛋白。证实了DNP介导的NPC细胞系（6-10B）的运动性和侵袭性。DNP处理后，26种磷酸化蛋白至少增加了1.5倍。通过蛋白质免疫印迹分析验证了所选磷酸化蛋白表达水平的变化。DNP处理改变了埃兹蛋白（苏氨酸567）、波形蛋白（丝氨酸55）、微管相关蛋白（丝氨酸25）和信号转导子和转录激活子3（丝氨酸727）的磷酸化。此外，研究表明，DNP依赖性转移部分是通过埃兹蛋白的苏氨酸567介导的，因为当埃兹蛋白的苏氨酸567发生突变时，DNP介导的转移减少。引人注目的是，NPC转移瘤中苏氨酸567磷酸化埃兹蛋白的表达高于原发肿瘤。这些发现为DNP诱导的NPC转移提供了新的见解，可能有助于更好地理解NPC肿瘤的转移机制。
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