TY - JOUR
T1 - Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma
AU - Yap, Lee Fah
AU - Velapasamy, Sharmila
AU - Lee, Hui Min
AU - Thavaraj, Selvam
AU - Rajadurai, Pathmanathan
AU - Wei, Wenbin
AU - Vrzalikova, Katerina
AU - Ibrahim, Maha Hafez
AU - Khoo, Alan Soo Beng
AU - Tsao, Sai Wah
AU - Paterson, Ian C.
AU - Taylor, Graham S.
AU - Dawson, Christopher W.
AU - Murray, Paul G.
N1 - Publisher Copyright:
© 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Epstein-Barr virus
KW - Lpa receptor
KW - Lysophosphatidic acid
KW - Nasopharyngeal carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84920742642&partnerID=8YFLogxK
U2 - 10.1002/path.4460
DO - 10.1002/path.4460
M3 - Article
C2 - 25294670
AN - SCOPUS:84920742642
SN - 0022-3417
VL - 235
SP - 456
EP - 465
JO - The Journal of Pathology
JF - The Journal of Pathology
IS - 3
ER -
