Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma

Research output: Contribution to journalArticle

Authors

  • Lee Fah Yap
  • Sharmila Velapasamy
  • Hui Min Lee
  • Selvam Thavaraj
  • Pathmanathan Rajadurai
  • Maha Hafez Ibrahim
  • Alan Soo-Beng Khoo
  • Sai Wah Tsao
  • Ian C Paterson

Abstract

Undifferentiated nasopharyngeal carcinoma (NPC) is a highly metastatic disease that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the contribution of lysophosphatidic acid (LPA) signalling to the pathogenesis of NPC. Here we demonstrate two distinct functional roles for LPA in NPC. First, we show that LPA enhances the migration of NPC cells and second, that it can inhibit the activity of EBV-specific cytotoxic T cells. Focusing on the first of these phenotypes, we show that one of the LPA receptors, LPA receptor 5 (LPAR5), is down-regulated in primary NPC tissues and that this down-regulation promotes the LPA-induced migration of NPC cell lines. Furthermore, we found that EBV infection or ectopic expression of the EBV-encoded LMP2A was sufficient to down-regulate LPAR5 in NPC cell lines. Our data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.

Bibliographic note

Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Details

Original languageEnglish
Pages (from-to)456-65
Number of pages10
JournalJournal of Pathology
Volume235
Issue number3
Publication statusPublished - Feb 2015

Keywords

  • Adenocarcinoma, Cell Line, Tumor, Cell Movement, Down-Regulation, Epstein-Barr Virus Infections, Gene Expression Regulation, Neoplastic, Herpesvirus 4, Human, Humans, Lysophospholipids, Nasopharyngeal Neoplasms, Phosphoric Diester Hydrolases, Receptors, Lysophosphatidic Acid, Signal Transduction, T-Lymphocytes, Cytotoxic, Viral Matrix Proteins