LMP1 promotes nasopharyngeal carcinoma metastasis through NTRK2-mediated anoikis resistance

摘要

Anoikis resistance is an important mechanism that mediates tumor metastasis. Studies have found that Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) promotes the occurrence, development, and metastasis of nasopharyngeal carcinoma (NPC). However, the related mechanism, especially whether LMP1 is involved in NPC metastasis through anoikis resistance, has not yet been elucidated. In present study, we showed that LMP1 enhanced the ability of NPC cells to resist anoikis by upregulating neurotrophic tyrosine kinase receptor type 2 (NTRK2 or TrkB) expression through NF-κB signaling and promoted the migration and invasion of NPC cells. After knockdown of NTRK2, the p-ERK and p-AKT in NPC cells were inhibited, and twist expression was further reduced, resulting in upregulation of E-cadherin expression and downregulation of vimentin expression. Subsequently, the results of a xenograft experiment showed that inhibiting NTRK2 could reduce LMP1-mediated NPC metastasis in vivo. In summary, these findings demonstrated that EBV-LMP1 upregulates twist expression to promote epithelial-mesenchymal transition (EMT) through the NTRK2-mediated AKT/ERK signaling pathway, thus mediating anoikis resistance and promoting NPC metastasis. These data will provide new molecular markers and potential targets for NPC metastasis.