Role for WNT16B in human epidermal keratinocyte proliferation and differentiation

Teh, Muy-Teck and Blaydon, Diana and Ghali, Lucy and Briggs, Victoria and Edmunds, Scott and Pantazi, Eleni and Barnes, Michael R. and Leigh, Irene M. and Kelsell, David P. and Philpott, Michael P. (2007) Role for WNT16B in human epidermal keratinocyte proliferation and differentiation. Journal of Cell Science, 120 (2). pp. 330-339. ISSN 0021-9533

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Official URL: http://dx.doi.org/10.1242/jcs.03329

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Abstract

WNT signalling regulates a variety of cell functions including cell fate, polarity, and differentiation via the canonical or -catenin stabilisation pathway and/or the planar cell polarity or non-canonical pathway. We have previously demonstrated that two isoforms (A and B) from the WNT16 locus have differential expression in various adult human tissues. In this study we show that WNT16B but not WNT16A isoform was upregulated in basal cell carcinomas compared with normal skin. We further investigated the cellular and molecular functions of WNT16B in primary human epidermal keratinocytes and a keratinocyte cell line. Cellular expression of WNT16B neither stabilised -catenin nor activated the lymphoid enhancer factor or T-cell factor transcriptional reporter in primary keratinocytes. WNT16B activated the Jun-N-terminal kinase cascade suggesting the activation of a non-canonical WNT signalling pathway. Constitutive expression of WNT16B significantly enhanced the rate of cell proliferation and prolonged clonogenicity in primary keratinocytes. Silencing WNT16B by RNA interference reduced keratinocyte proliferation. Furthermore, overexpression of WNT16B induced a hyperproliferation phenotype in an organotypical culture system. This work presents the first evidence that WNT16B activates human keratinocyte proliferation possibly via a -catenin-independent non-canonical WNT transduction pathway.

Item Type:Article
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PubMed PMID: 17200136

Erratum in: Journal of cell science. 2007 Mar 1;120(Pt 5):p.917.

Research Areas:Middlesex University Schools and Centres > School of Science and Technology > Natural Sciences
Middlesex University Schools and Centres > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
ID Code:2524
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Deposited On:18 Jun 2009 12:21
Last Modified:24 Oct 2014 15:39

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