Yin Yang 1 suppresses tumor invasion and metastasis in nasopharyngeal carcinoma by negatively regulating eIF4E transcriptional activity and expression.

Tumor metastasis is a leading cause of death in nasopharyngeal carcinoma (NPC) patients. Previous research has identified that transcription factor Yin Yang 1 (YY1) acts as a tumor suppressor that inhibits cell proliferation and tumor growth in NPC; however, the role and the molecular mechanisms of YY1 in NPC invasion and metastasis remain unclear. In this study, we discovered that YY1 could inhibit the migration and invasion of NPC cells in vitro as well as NPC xenograft tumor metastasis in vivo. Furthermore, we identified eIF4E as a direct downstream target of YY1, and YY1 could negatively regulate the expression of eIF4E at transcriptional level. Moreover, we found that eIF4E promoted the migration and invasion of NPC cells as well as NPC lung metastasis, suggesting its potential as a pro-metastatic mediator in NPC. Importantly, restoring eIF4E expression could partially reverse the inhibitory effects of YY1 on NPC malignancy. In consistent with these findings, the expression of YY1 was downregulated while eIF4E was upregulated in NPC patients with metastasis, and there was a negative correlation between YY1 and eIF4E expression. Collectively, our results indicate that YY1 suppresses the invasion and metastasis of NPC by negatively regulating eIF4E transcription. Therefore, targeting the YY1/eIF4E transcriptional axis could be a potential therapeutic strategy for the treatment of patients with NPC.