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
Authors: Yu Chen
Feiyan Zou
Chaojun Duan
Zhengke Peng
Wenhua Mei
Faqing Tang
Ya Cao
Zigang Dong
Yuan Wu
Xiaowei Tang
Damao Huang
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DNP; nasopharyngeal carcinoma; metastasis; ezrin phosphorylation; Rho kinase
Affiliations: Medical Research Center, Zhuhai Hospital, Guangzhou 510000, Guangdong, China. 

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. 

Retracted: No

PubPeer comments:
 Fig.7C In Fig.7C, Some features were removed from the second panel. Could the authors give explanation? ![file] , 
 Figure 5 has an image which appears in two other articles. This is part of a larger group of articles with numerous duplications. ![file] N,Nu0001-Dinitrosopiperazine-mediated Ezrin Protein Phosphorylation via Activation of Rho Kinase and Protein Kinase C Is Involved in Metastasis of Nasopharyngeal Carcinoma 6-10B Cells, J Biol Chem. 2011 Oct 2; 286(42): 36956--36967, doi:u00a010.1074 jbc.M111.259234, Figure 5 ![file] Berberine Inhibits Metastasis of Nasopharyngeal Carcinoma 5-8F Cells by Targeting Rho Kinase-mediated Ezrin Phosphorylation at Threonine 567, J Biol Chem. 2009 Oct 2; 284(40): 27456u2013-27466, doi:u00a010.1074 jbc.M109.033795, Figure 4 ![file] Dinitrosopiperazine-decreased PKP3 through upregulating miR-149 participates in nasopharyngeal carcinoma metastasis, Mol Carcinog. 2018 Dec, 57(12): 1763u2013-1779, doi:u00a010.1002 mc.22895, Figure 8 , 
 There is a second picture in Figure 5 which is also a duplication, appearing in two other articles. ![file] N,Nu0001-Dinitrosopiperazine-mediated Ezrin Protein Phosphorylation via Activation of Rho Kinase and Protein Kinase C Is Involved in Metastasis of Nasopharyngeal Carcinoma 6-10B Cells, J Biol Chem. 2011 Oct 2; 286(42): 36956--36967., doi:u00a010.1074 jbc.M111.259234, Figure 5 ![file] MNAT1 is overexpressed in colorectal cancer and mediates p53 ubiquitindegradation to promote colorectal cancer malignance, J Exp Clin Cancer Res. 2018; 37:284., doi:u00a010.1186 s13046-018-0956-3, Figure 8 ![file] N,Nu2019-Dinitrosopiperazineu2013Mediated Heat-Shock Protein 70-2 Expression Is Involved in Metastasis of Nasopharyngeal Carcinoma, PLoS One. 2013; 8(5): e62908, doi:u00a010.1371 journal.pone.0062908, Figure 6 , 
 The images in Figure 3 also appears in a second article with overlapping authors. ![file] N,Nu0001-Dinitrosopiperazine-mediated Ezrin Protein Phosphorylation via Activation of Rho Kinase and Protein Kinase C Is Involved in Metastasis of Nasopharyngeal Carcinoma 6-10B Cells, J Biol Chem. 2011 Oct 2; 286(42): 36956--36967, doi:u00a010.1074 jbc.M111.259234, Figure 3 ![file] Berberine Inhibits Metastasis of Nasopharyngeal Carcinoma 5-8F Cells by Targeting Rho Kinase-mediated Ezrin Phosphorylation at Threonine 567, J Biol Chem. 2009 Oct 2; 284(40): 27456u2013-27466, doi:u00a010.1074 jbc.M109.033795, Figure 2 ![file] Berberine Inhibits Metastasis of Nasopharyngeal Carcinoma 5-8F Cells by Targeting Rho Kinase-mediated Ezrin Phosphorylation at Threonine 567, J Biol Chem. 2009 Oct 2; 284(40): 27456u2013-27466, doi:u00a010.1074 jbc.M109.033795, Figure 7 , 
 Two parts of the blot in Figure 2 seem to appear also in the article [Peng et al. 2013] Figure 2. ![file] Tang et al. 2011 ![file] Peng et al. 2013 ,