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

Lee Fah Yap; Sharmila Velapasamy; Hui Min Lee; Selvam Thavaraj; Pathmanathan Rajadurai; Wenbin Wei; Katerina Vrzalikova; Maha Hafez Ibrahim; Alan Soo-Beng Khoo; Sai Wah Tsao; Ian C Paterson; Graham S Taylor; Christopher W Dawson; Paul G Murray

doi:10.1002/path.4460

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

Lee Fah Yap, Sharmila Velapasamy, Hui Min Lee, Selvam Thavaraj, Pathmanathan Rajadurai, Wenbin Wei, Katerina Vrzalikova, Maha Hafez Ibrahim, Alan Soo-Beng Khoo, Sai Wah Tsao, Ian C Paterson, Graham S Taylor, Christopher W Dawson, Paul G Murray

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15 Citations (Scopus)

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.

Original language	English
Pages (from-to)	456-65
Number of pages	10
Journal	Journal of Pathology
Volume	235
Issue number	3
DOIs	https://doi.org/10.1002/path.4460
Publication status	Published - Feb 2015

Bibliographical note

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

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Yap, L. F., Velapasamy, S., Lee, H. M., Thavaraj, S., Rajadurai, P., Wei, W., Vrzalikova, K., Ibrahim, M. H., Khoo, A. S-B., Tsao, S. W., Paterson, I. C., Taylor, G. S., Dawson, C. W., & Murray, P. G. (2015). Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma. Journal of Pathology, 235(3), 456-65. https://doi.org/10.1002/path.4460

@article{96dc0e9fdf104aae9062f7c82d600f65,

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

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.",

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",

author = "Yap, {Lee Fah} and Sharmila Velapasamy and Lee, {Hui Min} and Selvam Thavaraj and Pathmanathan Rajadurai and Wenbin Wei and Katerina Vrzalikova and Ibrahim, {Maha Hafez} and Khoo, {Alan Soo-Beng} and Tsao, {Sai Wah} and Paterson, {Ian C} and Taylor, {Graham S} and Dawson, {Christopher W} and Murray, {Paul G}",

note = "Copyright {\textcopyright} 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",

year = "2015",

month = feb,

doi = "10.1002/path.4460",

language = "English",

volume = "235",

pages = "456--65",

journal = "Journal of Pathology",

issn = "0022-3417",

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Yap, LF, Velapasamy, S, Lee, HM, Thavaraj, S, Rajadurai, P, Wei, W, Vrzalikova, K, Ibrahim, MH, Khoo, AS-B, Tsao, SW, Paterson, IC, Taylor, GS, Dawson, CW & Murray, PG 2015, 'Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma', Journal of Pathology, vol. 235, no. 3, pp. 456-65. https://doi.org/10.1002/path.4460

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

PY - 2015/2

Y1 - 2015/2

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 - Adenocarcinoma

KW - Cell Line, Tumor

KW - Cell Movement

KW - Down-Regulation

KW - Epstein-Barr Virus Infections

KW - Gene Expression Regulation, Neoplastic

KW - Herpesvirus 4, Human

KW - Humans

KW - Lysophospholipids

KW - Nasopharyngeal Neoplasms

KW - Phosphoric Diester Hydrolases

KW - Receptors, Lysophosphatidic Acid

KW - Signal Transduction

KW - T-Lymphocytes, Cytotoxic

KW - Viral Matrix Proteins

U2 - 10.1002/path.4460

DO - 10.1002/path.4460

M3 - Article

C2 - 25294670

SN - 0022-3417

VL - 235

SP - 456

EP - 465

JO - Journal of Pathology

JF - Journal of Pathology

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

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