LMP2A Enhances The Transformation Of MTA1 By Mediating The Activation Of MTOR And 4EBP1-eIF4E To Mediate The Transformation Of Epithelial Mesenchymal Transition Of Nasopharyngeal Carcinoma

Epstein-Barr Virus-encoded latent membrane protein 2A(LMP2A) promotes the epithelial-mesenchymal transition(EMT) of nasopharyngeal carcinoma(NPC), thereby increasing tumor invasion. Recently, the dysregulation of metastatic tumor antigen 1(MTA1) was found to enhance tumor metastasis in a variety of cancers. A molecular connection between these two proteins has been proposed but not firmly established. In this study, we report the overexpression of MTA1 in 29/60(48.3%) NPC patients and the overexpression of MTA1 significantly correlated with tumor metastasis. The overexpression of MTA1 promoted EMT via the Wnt1 pathway and β-catenin activation. We demonstrated that LMP2 A reinforces the expression of MTA1 via the mechanistic target of rapamycin(m TOR) pathway to promote EMT in NPC. Furthermore, knock-down of 4EBP1 combination with the new m TOR inhibitor INK-128 treatment, we discovered that LMP2 A expression activates the 4EBP1-e IF4 E axis and increases the expression of MTA1 at the translational level, partial independent of c-myc. These findings provide novel insights into the correlation between the LMP2 A and MTA1 proteins and reveal a novel function of the 4EBP1-e IF4 E axis in EMT in nasopharyngeal carcinoma.