Role for WNT16B in human epidermal keratinocyte proliferation and differentiation
Role for WNT16B in human epidermal keratinocyte proliferation and differentiation
复制标题
DOI：
10.1242/jcs.03329
复制
发表时间：
2007-01-15
影响因子：
4
通讯作者：
Philpott, Michael P.
中科院分区：
文献类型：
--
作者：
Teh, Muy-Teck;Blaydon, Diana;Philpott, Michael P.
WNT信号通过规范或β -连环蛋白稳定途径和/或平面细胞极性或非规范途径调节多种细胞功能，包括细胞命运、极性和分化。我们之前已经证明，来自WNT16基因座的两个亚型（A和B）在各种成人组织中具有差异表达。在这项研究中，我们发现与正常皮肤相比，WNT16B亚型而非WNT16A亚型在基底细胞癌中表达上调。我们进一步研究了WNT16B在原代人表皮角质形成细胞和角质形成细胞系中的细胞和分子功能。WNT16B的细胞表达既不能稳定β -连环蛋白，也不能激活原代角质形成细胞中的淋巴细胞增强因子或t细胞因子转录报告因子。WNT16B激活了jun - n末端激酶级联，提示激活了非典型的WNT信号通路。WNT16B的组成性表达显著提高了原代角质形成细胞的增殖率，延长了克隆原性。通过RNA干扰沉默WNT16B可降低角质细胞增殖。此外，在器官型培养系统中，过表达WNT16B诱导了过度增殖表型。这项工作首次证明WNT16B可能通过β -连环蛋白独立的非规范WNT转导途径激活人角质形成细胞增殖。
WNT signalling regulates a variety of cell functions including cell fate, polarity, and differentiation via the canonical or beta-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 beta-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 beta-catenin-independent non-canonical WNT transduction pathway.