Oncogene database

7474

WNT5A

wingless-type MMTV integration site family, member 5A;WNT5A;wingless-type MMTV integration site family, member 5A

WNT-5A protein|protein Wnt-5a

3p21-p14

protein-coding

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.

The highly conserved Wnt genes belong to a widely distributed family of presumptive signaling molecules that have been implicated not only in the regulation of normal pattern formation during embryogenesis and differentiation of cell lineages, but also in oncogenic events. ALL of the known vertebrate Wnt genes encode for 38- to 43-kDa cysteine-rich putative glycoproteins, which have features typical of secreted growth factors: a hydrophobic signal sequence, a conserved asparagine-linked oligosaccharide consensus sequence, and 22 conserved cysteine residues whose relative spacing is maintained. In this study, we report the cloning and sequencing of several overlapping cDNAs encoding approximately 4.1 kb of the human homologue of Wnt-5A. The mature protein contained 343 residues (M(r) approximately 38,000 excluding any post-translational modifications) with a > 93% homology to the reported sequences of other Wnt-5A proteins (> 99% homologous to mouse Wnt-5A). This protein maintained certain features--a hydrophobic signal sequence, the Wnt-1 family "signature sequence" (CKCHGvSGSC), and a number of other conserved amino acid residues: 24 cysteine residues, 4 asparagine-linked oligosaccharide consensus sequences, and a tyrosine sulfation site--that have been found in ALL other Wnt-5A proteins. Reverse transcriptase PCR analysis of RNA from a variety of human embryonic, neonatal, and adult cells and/or tissues showed that human Wnt-5A expression was detected only in neonatal heart and lung. It may be relevant, however, that the 3 -untranslated region contained numerous AT-rich motifs that could be involved in the rapid degradation of mRNA. Finally, using a combination of Southern blotting, PCR amplification, and in situ hybridization, the human Wnt-5A (WNT5A) gene was mapped to chromosome 3p14-p21.