Epstein-Barr Virus-Encoded Products Promote Circulating Tumor Cell Generation: A Novel Mechanism of Nasopharyngeal Carcinoma Metastasis.

Epstein-Barr virus (EBV) is a specific tumorigenic factor in the pathogenesis of nasopharyngeal carcinoma (NPC). Viral products encoded by EBV (LMP1, LMP2A, EBNA1, and miRNAs) have been shown to promote NPC metastasis. EBV-encoded oncoproteins and miRNAs have been shown to induce epithelial-mesenchymal transition (EMT) indirectly by inducing EMT transcription factors (EMT-TFs). These EBV-encoded products also promote the expression of EMT-TFs through post-transcriptional regulation. EMT contributes to generation of circulating tumor cells (CTCs) in epithelial cancers. CTCs exhibit stem cell characteristics, including increased invasiveness, enhanced cell intravasation, and improved cell survival in the peripheral system. EBV may contribute NPC metastasis through promoting generation of CTCs. Furthermore, CTC karyotypes are associated with NPC staging, therapeutic sensitivity, and resistance. We summarized studies showing that EBV-encoded virus-proteins and miRNAs promote generation of NPC CTCs, and highlighted the associated mechanism. This synthesis indicated that EBV mediates NPC metastasis through generation of CTCs.