Positive regulation of TAZ expression by EBV-LMP1 contributes to cell proliferation and epithelial-mesenchymal transition in nasopharyngeal carcinoma.

Jiang He,Jiang Li,Wenzheng Li,Liyu Liu,Lin Chen,Lun-Quan Sun,Deyun Feng,Zhi Li,Danming Ou,Lu Zhang,Feiyu Tang

doi:10.18632/oncotarget.13775

Abstract

The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression. Gelsolin is an important inhibitor of TAZ activity. Our studies showed that LMP1 interacted with gelsolin, resulting in inhibition of Lats1/2 phosphorylation and improvement of TAZ stability. Furthermore, we revealed that TAZ is important for LMP1-mediated cell proliferation, cancer stem cell-like properties and epithelial-mesenchymal transition. These findings provide new insights into the carcinogenic roles of LMP1 and contribute to further understanding of its oncogenic mechanism.

Highlights

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus which is involved in many human malignancies, such as nasopharyngeal carcinoma (NPC), Burkitt’s lymphoma, T-cell lymphoma, gastric carcinoma, and invasive breast cancer [1, 2]
The results showed that the level of TAZ protein increased in CNE1-latent membrane protein 1 (LMP1) and CNE2-LMP1 cells compared with their control cells (Figure 1A and 1B)
LMP1 is a constitutively active pseudo-receptor that acts as a key player during B cell immortalization [44]

Summary

Introduction

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus which is involved in many human malignancies, such as nasopharyngeal carcinoma (NPC), Burkitt’s lymphoma, T-cell lymphoma, gastric carcinoma, and invasive breast cancer [1, 2]. Constant EBV infection can efficiently transform resting B cells into permanently growing lymphoblastoid cell lines in vitro. The latent membrane protein 1 (LMP1), a 62-kDa integral membrane protein, is one of the most important oncogenic proteins of human DNA tumor virus EBV. CTAR1 and CTAR2 have been reported to be involved in the induction of NF-κB transcription factor pathway [5]. The ability that LMP1 immortalizes and transforms cells is most likely associated with simultaneously controlling cellular signaling pathways that block apoptosis or mediate proliferative, growth factor-like effects. LMP1 could induce a cancer progenitor cells (CPC)-like phenotype in epithelial cells, suggesting that www.impactjournals.com/oncotarget

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