title: 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.
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 kinase C (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.
authors: Medical Research Center, Zhuhai Hospital, Guangzhou 510000, Guangdong, China. tangfaqing33@hotmail.com
authors: Faqing
authors: F
authors: Tang
authors: Feiyan
authors: F
authors: Zou
authors: Zhengke
authors: Z
authors: Peng
authors: Damao
authors: D
authors: Huang
authors: Yuan
authors: Y
authors: Wu
authors: Yu
authors: Y
authors: Chen
authors: Chaojun
authors: C
authors: Duan
authors: Ya
authors: Y
authors: Cao
authors: Wenhua
authors: W
authors: Mei
authors: Xiaowei
authors: X
authors: Tang
authors: Zigang
authors: Z
authors: Dong
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009602:Nitrosamines / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D014183:Transplantation, Heterologous; D054460:rho-Associated Kinases / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D002273:Carcinogens; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D009602:Nitrosamines; D011493:Protein Kinase C; D054460:rho-Associated Kinases; D000099149:Ezrin; C026156:N,N'-dinitrosopiperazine