N,N′-Dinitrosopiperazine-mediated ezrin protein phosphorylation via activation of rho kinase and protein kinase C is involved in metastasis of nasopharyngeal carcinoma 6-10B cells

Faqing Tang, Feiyan Zou, Zhengke Peng, Damao Huang, Yuan Wu, Yu Chen, Chaojun Duan, Ya Cao, Wenhua Mei, Xiaowei Tang, Zigang Dong

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

N,N′-Dinitrosopiperazine (DNP) is a carcinogen for nasopharyngeal carcinoma (NPC), which shows organ specificity to nasopharyngeal epithelium. Herein, we demonstrate that DNP induces fiber formation of NPC cells (6-10B) and also increases invasion and motility of 6-10B cells. DNP-mediated NPC metastasis also was confirmed in nude mice. Importantly, DNP induced the expression of phosphorylated ezrin (phos-ezrin) at threonine 567 (Thr-567) dose- and time-dependently but had no effect on the total ezrin expression at these concentrations. Furthermore, DNP-induced phos-ezrin expression was dependent on increased Rho kinase and protein kinaseC(PKC) activity. DNP may activate Rho kinase through binding to its pleckstrin homology and may activate PKC through promoting its translocation to the plasma membrane in vivo. DNP-induced phos-ezrin was associated with induction of fiber growth in 6-10B cells. However, DNP could not induce motility and invasion of NPC cells containing ezrin mutated at Thr-567. Similarly, DNP could not induce motility and invasion of the cells containing siRNAs against Rho or PKC. These results indicate that DNP induces ezrin phosphorylation at Thr-567, increases motility and invasion of cells, and promotes tumor metastasis. DNP may be involved in NPC metastasis through regulation of ezrin phosphorylation at Thr-567.

Original languageEnglish (US)
Pages (from-to)36956-36967
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number42
DOIs
StatePublished - Oct 21 2011

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