Dinitrosopiperazine-mediated phosphorylated-proteins are involved in nasopharyngeal carcinoma metastasis.
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.
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China. tgj1129@163.com.
Gongjun
G
Tan
Metallurgical Science and Engineering, Central South University, 21 Lushan South Road, Changsha 410083, China. tangxw19907@hotmail.com.
Xiaowei
X
Tang
Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China. huangdamao@hotmail.com.
Damao
D
Huang
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China. liyuejincat@163.com.
Yuejin
Y
Li
Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China. liuna8542@163.com.
Na
N
Liu
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China. pengzhengke@126.com.
Zhengke
Z
Peng
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China. fromzhenlin@foxmail.com.
Zhenlin
Z
Zhang
Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China. duancjxy@126.com.
Chaojun
C
Duan
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China. lujinping_2006@163.com.
Jinping
J
Lu
Institute of Life and Health Engineering, National Engineering and Research Center for Genetic Medicine, Jinan University, 601 Huangpu Road West, Guangzhou 510632, China. jxygr007@126.com.
Guangrong
G
Yan
Medical Research Center and Clinical Laboratory, Zhuhai Hospital of Jinan University, 79 Kangning Road, Zhuhai 519000, China. tangfaqing33@hotmail.com.
Faqing
F
Tang
D015153:Blotting, Western; D002277:Carcinoma; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D013058:Mass Spectrometry; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009602:Nitrosamines / Q000737:chemistry / Q000633:toxicity*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D009602:Nitrosamines; D010750:Phosphoproteins; D010769:Phosphothreonine; D000099149:Ezrin; C026156:N,N'-dinitrosopiperazine