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 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.
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
Yuejin
Y
Li
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
Jinping
J
Lu
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
Zhengke
Z
Peng
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
Gongjun
G
Tan
Medical Research Center and Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Na
N
Liu
Medical Research Center and Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Damao
D
Huang
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
Zhenlin
Z
Zhang
Medical Research Center and Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Chaojun
C
Duan
Metallurgical Science and Engineering, Central South University, Changsha, People's Republic of China.
Xiaowei
X
Tang
Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, Guangdong, People's Republic of China.
Faqing
F
Tang
D002277:Carcinoma; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology*; D009088:Mucoproteins; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009602:Nitrosamines / Q000009:adverse effects*; D015513:Oncogene Proteins; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
C502296:AGR2 protein, human; D009088:Mucoproteins; D009602:Nitrosamines; D015513:Oncogene Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D002401:Cathepsin B; D002402:Cathepsin D; C026156:N,N'-dinitrosopiperazine