Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells
Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells
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DOI：
10.1111/j.1349-7006.2003.tb01488.x
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发表时间：
2003-07-01
期刊：
影响因子：
5.7
通讯作者：
Nagayama, M
中科院分区：
文献类型：
--
作者：
Taki, M;Kamata, N;Nagayama, M
应用逆转录聚合酶链式反应(RT-PCR)检测了11株鳞癌细胞系中WNT-1、2、3、4、5a、6和7a基因的表达，并与2株正常口腔角质形成细胞系进行了比较。WNT-4和WNT-5a的表达呈负相关，即WNT-4在HOC719-NE、HOC313和TSU细胞中不表达，而WNT-5a仅在这些细胞中强表达。这些细胞株E-钙粘蛋白表达降低，波形蛋白表达增强，同时伴有Snail和deltaEF1的强烈表达，这两种基因被认为是E-钙粘素的反式阻滞剂，并触发了上皮-间充质转化(EMT)，提示Wnt-4与SCC细胞的上皮表型有关，Wnt-5a与SCC细胞的间质表型有关。为了研究这些Wnt基因的表达是否受EMT的调控，我们将Snail表达载体导入表达Wnt-4而不表达Wnt-5a的A431和OM-1细胞。稳定表达Snail的克隆表现为梭形细胞形态，波形蛋白表达增加，E-钙粘蛋白表达降低，同时deltaEF1表达增强。在这些克隆中，WNT-4表达下调，WNT-5a表达上调。提示EMT对WNT-4和WNT-5a的影响相反，WNT-4的下调和WNT-5a的上调可能是人鳞状细胞癌恶性表型的标志。
Gene expression of Wnt-1, 2, 3, 4, 5a, 6 and 7a was analyzed by RTPCR in eleven squamous cell carcinoma (SCC) cell lines and compared with that in two normal oral keratinocyte strains. There appeared to be an inverse relationship between Wnt-4 and Wnt-5a expressions, i.e., Wnt-4 was not expressed in HOC719-NE, HOC313 or TSU cells, while Wnt-5a was strongly expressed only in these cells. These cell lines showed decreased expression of E-cadherin and elevated expression of vimentin accompanied with strong expressions of Snail and deltaEF1, which have been reported to be transrepressors of E-cadherin and to trigger epithelial-mesenchymal transition (EMT), suggesting associations of Wnt-4 with epithelial phenotype and Wnt-5a with mesenchymal phenotype of SCC cells. To study whether the expressions of these Wnt genes are regulated by EMT, we transfected a Snail-expression vector into A431 and OM-1 cells, which express Wnt-4 but not Wnt-5a. The stably Snail-overexpressing clones showed spindle morphology, increased expression of vimentin and decreased expression of E-cadherin accompanied with augmented expression of deltaEF1. In these clones, down-regulation of Wnt-4 and up-regulation of Wnt-5a were clearly observed. These results indicated that Wnt-4 and Wnt-5a are oppositely affected by EMT, and down-regulation of Wnt-4 and up-regulation of Wnt-5a are possible markers of the malignant phenotype of human SCC.