N,N'-dinitrosopiperazine-mediated AGR2 is involved in metastasis of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) has a high metastatic character in the clinic, but its mechanism is not clear. As a carcinogen with organ specificity for the nasopharyngeal epithelium, N,N'-Dinitrosopiperazine (DNP) is involved in NPC metastasis. Herein, our data revealed that anterior gradient...

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Bibliographic Details
Published in:PloS one 2014-04, Vol.9 (4), p.e92081
Main Authors: Li, Yuejin, Lu, Jinping, Peng, Zhengke, Tan, Gongjun, Liu, Na, Huang, Damao, Zhang, Zhenlin, Duan, Chaojun, Tang, Xiaowei, Tang, Faqing
Format: Article
Language:English
Subjects:
Apoptosis
B cells
Biology and Life Sciences
Breast cancer
Carcinogens
Carcinoma
Care and treatment
Cathepsin B - metabolism
Cathepsin D - metabolism
Cell cycle
Cell Line, Tumor
Cell Movement
Cervix
Colorectal cancer
Development and progression
Enzymes
Epithelium
Epithelium - metabolism
Epithelium - pathology
Ethics
Extracellular matrix
Genetic aspects
Humans
Immunohistochemistry
Laboratories
Lymph nodes
Lymphatic Metastasis - pathology
Lymphatic system
Medical prognosis
Medical research
Medicine and Health Sciences
Metastases
Metastasis
Motility
Nasopharyngeal cancer
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms - enzymology
Nasopharyngeal Neoplasms - metabolism
Nasopharyngeal Neoplasms - pathology
Neoplasm Invasiveness
Nitrosamines - adverse effects
Pancreatic cancer
Patient outcomes
Physical Sciences
Physiological aspects
Protein Binding
Proteins - metabolism
Risk factors
RNA, Small Interfering - metabolism
siRNA
Throat cancer
Tissues
Urine
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Summary:Nasopharyngeal carcinoma (NPC) has a high metastatic character in the clinic, but its mechanism is not clear. As a carcinogen with organ specificity for the nasopharyngeal epithelium, N,N'-Dinitrosopiperazine (DNP) is involved in NPC metastasis. Herein, our data revealed that anterior gradient 2 (AGR2) was overexpressed in human NPC tissues, particularly in cervical lymph node metastatic NPC (LMNPC). High AGR2 expression was associated with NPC metastasis. Importantly, DNP induced AGR2 expression, and increased cell motility and invasion in the NPC cell line 6-10B. However, DNP-mediated cell motility and invasion was dramatically decreased when transfected with siRNA-AGR2. Further, AGR2 directly regulated cathepsin (CTS) B and D by binding them in vitro. These results indicate that DNP induces AGR2 expression, regulates CTSB and CTSD, increases cell motility and invasion, and promotes NPC tumor metastasis. Therefore, DNP-mediated AGR2 expression may be an important factor in prolific NPC metastasis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0092081