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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >WNT7a induces E-cadherin in lung cancer cells.
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WNT7a induces E-cadherin in lung cancer cells.

机译：WNT7a在肺癌细胞中诱导E-钙粘着蛋白。

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E-cadherin loss in cancer is associated with de-differentiation, invasion, and metastasis. Drosophila DE-cadherin is regulated by Wnt/beta-catenin signaling, although this has not been demonstrated in mammalian cells. We previously reported that expression of WNT7a, encoded on 3p25, was frequently downregulated in lung cancer, and that loss of E-cadherin or beta-catenin was a poor prognostic feature. Here we show that WNT7a both activates E-cadherin expression via a beta-catenin specific mechanism in lung cancer cells and is involved in a positive feedback loop. Li+, a GSK3 beta inhibitor, led to E-cadherin induction in an inositol-independent manner. Similarly, exposure to mWNT7a specifically induced free beta-catenin and E-cadherin. Among known transcriptional suppressors of E-cadherin, ZEB1 was uniquely correlated with E-cadherin loss in lung cancer cell lines, and its inhibition by RNA interference resulted in E-cadherin induction. Pharmacologic reversal of E-cadherin and WNT7a losses was achieved with Li+, histone deacetylase inhibition, or in some cases only with combined inhibitors. Our findings provide support that E-cadherin induction by WNT/beta-catenin signaling is an evolutionarily conserved pathway operative in lung cancer cells, and that loss of WNT7a expression may be important in lung cancer development or progression by its effects on E-cadherin.
机译：癌症中E-钙粘蛋白的丢失与去分化，侵袭和转移有关。果蝇DE-钙黏着蛋白受Wnt /β-catenin信号传导调节，尽管尚未在哺乳动物细胞中得到证实。我们先前曾报道，在肺癌中经常编码3p25的WNT7a表达，而E-钙粘蛋白或β-连环蛋白的丢失是不良的预后特征。在这里，我们显示WNT7a既可以通过β-catenin特异性机制激活肺癌细胞中的E-cadherin表达，又可以参与正反馈回路。 Li +，一种GSK3β抑制剂，以肌醇非依赖性方式诱导E-钙粘着蛋白。同样，暴露于mWNT7a会特异性诱导游离β-catenin和E-cadherin。在已知的E-钙粘蛋白转录抑制因子中，ZEB1与肺癌细胞株中E-钙粘蛋白的丢失具有独特的相关性，并且它的RNA干扰抑制作用导致E-钙粘蛋白的诱导。 E +钙粘蛋白和WNT7a的药理逆转通过Li +，组蛋白脱乙酰基酶的抑制或在某些情况下仅通过联合抑制剂来实现。我们的发现提供了支持，即通过WNT /β-catenin信号传导诱导E-钙粘着蛋白是在肺癌细胞中可操作的进化保守途径，并且WNT7a表达的丧失可能通过其对E-钙粘着蛋白的作用在肺癌的发展或进展中很重要。

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