N,N'-dinitrosopiperazine--mediated heat-shock protein 70-2 expression is involved in metastasis of nasopharyngeal carcinoma
Authors: Yuejin Li
Chaojun Duan
Zhengke Peng
Wenhua Mei
Faqing Tang
Na Liu
Xiaowei Tang
Feng Zhu
Damao Huang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: N,N'-Dinitrosopiperazine; nasopharyngeal carcinoma; metastasis; heat-shock protein; HSP70-2
Affiliations: Medical Research Center and Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, People's Republic of China.

Abstract:  N,N'-Dinitrosopiperazine (DNP) is invovled in nasopharyngeal carcinoma (NPC) development and metastasis, and it shows organ specificity to the nasopharyngeal epithelium. Herein, we demonstrate that DNP induces heat-shock protein (HSP) 70-2 expression in NPC cells (6-10B) at a non-cytotoxic concentration. DNP induced HSP70-2 expression in a dose- and time- dependent manner, but showed no effect on other HSP70 family members. Furthermore, DNP also increased HSP70-2 RNA transcription through directly binding to the hypoxia-responsive elements (HRE) and heat shock elements (HSE) located in the HSP70-2 promoter. DNP-mediated HSP70-2 expression might act through enhancing the transcription of HSP70-2 RNA. Importantly, DNP induced motility and invasion of 6-10B cells dose- and time-dependently, and DNP-mediated NPC metastasis was confirmed in nude mice, which showed high HSP70-2 expression in the metastatic tumor tissue. However, the motility and invasion of NPC cells that were stably transfected using short interfering RNA against HSP70-2 could not effectively induce DNP. These results indicate that DNP induces HSP70-2 expression through increasing HSP70-2 transcription, increases the motility and invasion of cells, and promotes NPC tumor metastasis. Therefore, DNP mediated HSP70-2 expression may be an important factor of NPC-high metastasis. 

Retracted: No

PubPeer comments:
 One of the images in Figure 6 is a duplicate with a picture in a second article with overlapping authors. This is part of a large group of articles with numerous duplicated pictures. ![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. ![file] Identification of novel signaling components in N,Nu2019-Dinitrosopiperazine-mediated metastasis of nasopharyngeal Carcinoma by quantitative phosphoproteomics, BMC Cancer 2014, 14:243, doi:u00a010.1186 1471-2407-14-243, Figure 8. , 
 There are two more picture in Figure 6 which are duplicates. ![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 ![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,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 , 
 One of the images in Figure 4 appears in multiple articles. I have included here, for context, picture from five different articles, with in total 6 pictures appearing multiple times. ![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 4 ![file] Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis, Oncotarget. 2016 Feb 9; 7(6): 7012--7028., doi:u00a010.18632 oncotarget.6875, Figure 2 ![file] Identification of novel signaling components in N,Nu2019-Dinitrosopiperazine-mediated metastasis of nasopharyngeal Carcinoma by quantitative phosphoproteomics, BMC Cancer 2014, 14:243., doi:u00a010.1186 1471-2407-14-243, Figure 2 ![file] Dinitrosopiperazine-Mediated Phosphorylated-Proteins Are Involved in Nasopharyngeal Carcinoma Metastasis, Int. J. Mol. Sci. 2014 Nov; 15(11), 20054--20071., doi:u00a010.3390 ijms151120054, Figure 2 ![file] Proteomic analysis on N, N0 -dinitrosopiperazinemediated metastasis of nasopharyngeal carcinoma 6-10B cells, BMC Biochem. 2012; 13:25., doi:u00a010.1186 1471-2091-13-25, Figure 3 , 
 In addition, two more images in Figure 4 appears in a second article. ![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 4 ![file] N,N9-Dinitrosopiperazine-Mediated AGR2 Is Involved in Metastasis of Nasopharyngeal Carcinoma, PLoS ONE. 2014; 9(4): e92081., doi:u00a010.1371 journal.pone.0092081, Figure 4 , 
 The blots in Figure 2 contains what looks to be a duplication. In addition, two parts of the blots seem to appear also in the article [Tang et al. 2011] Figure 2. ![file] Peng et al. 2013 ![file] Tang et al. 2011 ,