Clusterin induced by N,N'-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis.
Clusterin induced by N,N'-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis.
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DOI：
10.18632/oncotarget.6750
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发表时间：
2016-02-02
期刊：
影响因子：
--
通讯作者：
Tang F
中科院分区：
文献类型：
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作者：
Li Y;Lu J;Zhou S;Wang W;Tan G;Zhang Z;Dong Z;Kang T;Tang F
鼻咽癌（Nasopharyngealcarcinoma，NPC）具有高转移的临床病理特征。N，N′-二亚硝基哌嗪（DNP）作为一种致癌因子，参与了鼻咽癌的转移，但其确切机制尚未完全阐明。在此，我们发现DNP通过上调前簇蛋白（CLU）促进NPC转移。DNP可上调CLU、基质金属蛋白酶9（MMP-9）和血管内皮生长因子（VEGF）的表达和活性，进一步上调MMP-9和VEGF的表达。我们还发现，DNP增加CLU与MMP-9或VEGF的结合。DNP可诱导鼻咽癌细胞的运动和侵袭能力，siRNA-CLU可抑制DNP诱导的鼻咽癌细胞运动和侵袭能力。临床研究表明，CLU、MMP-9和VEGF与肿瘤淋巴结转移（TNM）分级呈正相关。提示DNP可能通过上调CLU、MMP-9和VEGF的表达而促进鼻咽癌的转移。因此，DNP增加的CLU表达可能是NPC高转移的重要因素，CLU可作为NPC转移的生物标志物。
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.