title: Oncogenic effects of WNT5A in Epstein-Barr virus‑associated nasopharyngeal carcinoma.
abstract: The molecular events that drive the progression of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) are still to be elucidated. Here, we report for the first time the pathogenic significance of an NPC-associated gene, wingless-type MMTV integration site family, member 5A (WNT5A) and the contribution of EBV to its expression. WNT5A is a representative Wnt protein that activates non-canonical Wnt signalling. With regard to its role in carcinogenesis, there is conflicting evidence as to whether WNT5A has a tumour-promoting or tumour-suppressive role. We show that WNT5A is upregulated in primary NPC tissue samples. We also demonstrate that WNT5A expression was dramatically increased in NPC cell lines expressing the EBV-encoded LMP2A gene, suggesting that this EBV-encoded latent gene is responsible for upregulating WNT5A in NPC. In addition, in vitro WNT5A overexpression promotes the proliferation, migration and invasion of NPC cells. Our results not only reveal pro-tumorigenic effects of WNT5A in NPC but also suggest that WNT5A could be an important therapeutic target in patients with EBV-associated disease.
authors.affiliation: Department of Oral Biology and Biomedical Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.affiliation: Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Munirah
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Cancer Research Initiatives Foundation, Selangor, Malaysia.
authors.forename: Muhammad Mamduh Ahmad
authors.initials: MM
authors.lastname: Zabidi
authors.affiliation: Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Tai Lin
authors.initials: TL
authors.lastname: Chu
authors.affiliation: Cancer Research Initiatives Foundation, Selangor, Malaysia.
authors.forename: San Jiun
authors.initials: SJ
authors.lastname: Chai
authors.affiliation: Department of Oral Biology and Biomedical Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Tung Shin Hospital, Kuala Lumpur, Malaysia.
authors.forename: Paul Vey Hong
authors.initials: PV
authors.lastname: Lim
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dawson
authors.affiliation: Cancer Research Initiatives Foundation, Selangor, Malaysia.
authors.forename: Soo-Hwang
authors.initials: SH
authors.lastname: Teo
authors.affiliation: Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Alan Soo Beng
authors.initials: AS
authors.lastname: Khoo
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011518:Proto-Oncogene Proteins; D014763:Viral Matrix Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein