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PLoS One. 2014 Apr 9;9(4):e92081. doi: 10.1371/journal.pone.0092081. eCollection 2014.

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

Author information

1
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
2
Medical Research Center and Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
3
Metallurgical Science and Engineering, Central South University, Changsha, People's Republic of China.

Abstract

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.

PMID:
24717913
PMCID:
PMC3981702
DOI:
10.1371/journal.pone.0092081
[Indexed for MEDLINE]
Free PMC Article
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