P0033 N,N′-dinitrosopiperazine-mediated AGR2 in metastasis of nasopharyngeal carcinoma

Abstract

Background Nasopharyngeal carcinoma (NPC) has a highly metastatic character in the clinic, but the underlying mechanism of action is unclear. N,N′-dinitrosopiperazine (DNP), a carcinogen with organ specificity for the nasopharyngeal epithelium, is involved in metastasis of NPC. Findings Anterior gradient 2 (AGR2) was overexpressed in human NPC tissues, especially in cervical lymph node metastatic NPC (LMNPC). High AGR2 expression was associated with NPC metastasis. 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 substantially decreased when transfected with siRNA-AGR2. Furthermore, AGR2 directly regulated cathepsin B and D by binding them in vitro. Interpretation These results indicate that DNP induces AGR2 expression, regulates cathepsin B and D, increases cell motility and invasion, and promotes NPC tumour metastasis. Therefore, DNP-mediated AGR2 expression may be an important factor in prolific NPC metastasis.