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

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

doi:10.18632/oncotarget.13775

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

Oncotarget. 2016 Dec 2;8(32):52333-52344. doi: 10.18632/oncotarget.13775. eCollection 2017 Aug 8.

Authors

Jiang He^{1

2}, Feiyu Tang¹, Liyu Liu^{1

2}, Lin Chen¹, Jiang Li¹, Danming Ou¹, Lu Zhang^{1

2}, Zhi Li^{1

2}, Deyun Feng³, Wenzheng Li⁴, Lun-Quan Sun^{1

2}

Affiliations

¹ Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410008, China.
² Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, 410008, China.
³ Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, China.
⁴ Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410008, China.

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.

Keywords: EBV; LMP1; TAZ; nasopharyngeal carcinoma.