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Int J Oncol. 2014 May;44(5):1774-80. doi: 10.3892/ijo.2014.2342. Epub 2014 Mar 13.

Oncogenic effects of WNT5A in Epstein-Barr virus‑associated nasopharyngeal carcinoma.

Author information

1
Department of Oral Biology and Biomedical Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
2
Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
3
Cancer Research Initiatives Foundation, Selangor, Malaysia.
4
Tung Shin Hospital, Kuala Lumpur, Malaysia.
5
School of Cancer Sciences, University of Birmingham, Birmingham, UK.

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.

PMID:
24626628
DOI:
10.3892/ijo.2014.2342
[Indexed for MEDLINE]
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