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.
authors.affiliation: Department of Oral Biology & Biomedical Sciences and Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.forename: Sharmila
authors.initials: S
authors.lastname: Velapasamy
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Lee
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.forename: Pathmanathan
authors.initials: P
authors.lastname: Rajadurai
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.forename: Katerina
authors.initials: K
authors.lastname: Vrzalikova
authors.forename: Maha Hafez
authors.initials: MH
authors.lastname: Ibrahim
authors.forename: Alan Soo-Beng
authors.initials: AS
authors.lastname: Khoo
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Ian C
authors.initials: IC
authors.lastname: Paterson
authors.forename: Graham S
authors.initials: GS
authors.lastname: Taylor
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Dawson
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology*; D020031:Epstein-Barr Virus Infections / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D014763:Viral Matrix Proteins / Q000502:physiology; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D014763:Viral Matrix Proteins; D000099189:Lysophospholipase D; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C512992:LPAR5 protein, human; C032881:lysophosphatidic acid
keywords: Epstein-Barr virus; LPA receptor; lysophosphatidic acid; nasopharyngeal carcinoma