Research Papers:

Clusterin induced by N,N’-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis

Yuejin Li, Jinping Lu, Shan Zhou, Weiwei Wang, Gongjun Tan, Zhenlin Zhang, Zigang Dong, Tiebang Kang and Faqing Tang _

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Oncotarget. 2016; 7:5548-5563. https://doi.org/10.18632/oncotarget.6750

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Yuejin Li1,2,*, Jinping Lu2,*, Shan Zhou2,*, Weiwei Wang2, Gongjun Tan2, Zhenlin Zhang2, Zigang Dong3, Tiebang Kang1, Faqing Tang2

1State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China

2Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People’s Hospital, Zhuhai 519000, Guangdong, China

3Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA

*These authors have contributed equally to this work

Correspondence to:

Faqing Tang, e-mail: [email protected]

Tiebang Kang e-mail: [email protected]

Keywords: N,N′-Dinitrosopiperazine, clusterin, nasopharyngeal carcinoma, metastasis

Received: September 03, 2015     Accepted: December 07, 2015     Published: December 24, 2015


Nasopharyngeal carcinoma (NPC) has a high metastatic clinicopathological feature. As a carcinogen factor, N,N′-Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its precise mechanism has not been fully elucidated. Herein, we showed that DNP promotes NPC metastasis through up-regulating anterior clusterin (CLU). DNP was found to increase CLU, matrix metalloproteinases (MMP) 9 and vascular endothelial growth factor (VEGF) expression and activity, further DNP-increased MMP-9 and VEGF expression was through up-regulating CLU. We also found that DNP increased the binding of CLU with MMP-9 or VEGF. DNP induced the motility and invasion of NPC cell, which was inhibited by siRNA-CLU. The clinical investigation showed that CLU, MMP-9 and VEGF were positively correlated with the tumor-node -metastasis (TNM) classification. These results indicate that DNP may promote NPC tumor metastasis through up-regulating CLU, MMP-9 and VEGF expression. Therefore, DNP-increased CLU expression may be an important factor of NPC-high metastasis, and CLU may serve as a biomarker for NPC metastasis.

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