LMP1 Up-regulates Calreticulin to Induce Epithelial-mesenchymal Transition via TGF-β/Smad3/NRP1 Pathway in Nasopharyngeal Carcinoma Cells

Background: Latent membrane protein 1 (LMP1) is known as an oncogenic protein encoded by the EBV genome. The purpose of this study was to investigate the mechanism of LMP1-induced cell epithelial-mesenchymal transition (EMT). Methods: The NP69 cell line of nasopharyngeal epithelial cells with high expression of LMP1 was established to observe the effect of high expression of LMP1 on cell growth, proliferation, cycle, apoptosis, migration and invasion. We used proteomics to screen and identify differentially expressed proteins related to LMP1-mediated epithelial cell transformation. Then, we analyzed the expression and significance of differentially expressed calreticulin (CRT) in nasopharyngeal carcinoma (NPC), and observed the effect of CRT expression on EMT in CNE2 cells of NPC. Finally, the expression of neuropilin-1 (NRP1), which is a protein downstream of the EMT-related signaling pathway TGF-β (transforming growth factor β), was detected. Results: LMP1 promoted NP69 cells proliferation, inhibited apoptosis and induced EMT. We identified 22 differentially expressed proteins associated with LMP1-induced EMT. Among them, CRT expression level was significantly increased in NPC compared with adjacent tissues, and was interrelated with TNM staging and lymph node metastasis of NPC. After knockdown of CRT expression, the phenomenon of cell EMT was reduced and the ability of cell migration and invasion was weakened. CRT regulated NRP1 expression by affecting SMAD3 phosphorylation. Conclusion: LMP1 induced cell EMT via TGF-β/Smad3/NRP1 pathway, which promoted migration and invasion of NPC cells.