Epstein-Barr virus LMP1 promotes tumorigenesis in a murine epithelial tumor model

Epstein-Barr virus (EBV), an oncogenic herpesvirus, is associated with diverse epithelial and lymphatic malignancies. The latent membrane protein 1 (LMP1) is well-established as a key oncogenic driver in B-cell malignancies, while its functional role in epithelial tumors remains poorly understood. This study aimed to establish an epithelial tumor model stably expressing LMP1 and investigate its oncogenic functions and mechanisms. We generated mouse lung epithelial cells TC-1 stably expressing EBV LMP1 using the PiggyBac transposon system (TC-1-LMP1). The TC-1-LMP1 model demonstrated that LMP1 enhanced proliferative and invasive capacities while reducing cell adhesion in <i>vitro</i>, and promotes aggressive tumor growth in <i>vivo</i>. RNA-seq analysis revealed that LMP1 increased the expression of Myc, leading to enhanced ribosome biogenesis and mitochondrial metabolic reprogramming. Our findings demonstrate that LMP1 act as a potent oncogenic driver in epithelial cells by regulating the expression and function of Myc, thereby advancing the understanding of the mechanism underlying EBV-associated epithelial tumorigenesis. The TC-1-LMP1 model could also serve as a valuable platform for investigating LMP1-targeted therapeutic strategies.