N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1
N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1
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DOI：
10.1158/0008-5472.can-05-3401
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Heimark, RL
中科院分区：
文献类型：
--
作者：
Alexander, NR;Tran, NL;Heimark, RL
已经证明，在癌中N-钙粘蛋白表达的获得在细胞迁移、侵袭和存活的调节中是重要的。在这里，我们表明，在PC-3前列腺癌细胞中的N-钙粘蛋白mRNA的表达依赖于01整合素介导的细胞粘附到纤连蛋白和基本的螺旋-环-螺旋转录因子Twist 1。Twist 1 mRNA的小干扰RNA的消耗导致Twist 1和N-cadherin的表达降低和细胞迁移的抑制。而Twist 1基因表达是独立的β（1）整合素介导的粘附，Twist 1蛋白未能积累在细胞核中培养的锚定非依赖性条件。Twist 1细胞附着后增加的核积累被Rho激酶抑制剂或0，整联蛋白中和抗体抑制。Twist 1对N-cadherin mRNA诱导的作用需要位于N-cadherin基因第一内含子（+2，627）内的E-box顺式元件。这些数据提出了这样的可能性，即在转移过程中整合素介导的粘附间质基质蛋白差异调节Twist 1的核/胞质易位和DNA结合，激活N-钙粘蛋白转录。
The gain of N-cadherin expression in carcinomas has been shown to be important in the regulation of cell migration, invasion, and survival. Here, we show that N-cadherin mRNA expression in PC-3 prostate carcinoma cells is dependent on 01 integrin-mediated cell adhesion to fibronectin and the basic helix-loop-helix transcription factor Twist1. Depletion of Twist1 mRNA by small interfering RNA resulted in decreased expression of both Twist1 and N-cadherin and the inhibition of cell migration. Whereas Twist1 gene expression was independent of beta(1) integrin-mediated adhesion, Twist1 protein failed to accumulate in the nuclei of cells cultured in anchorage-independent conditions. The increased nuclear accumulation of Twist1 following cell attachment was suppressed by treatment with an inhibitor of Rho kinase or a 0, integrin neutralizing antibody. The effect of Twist1 on induction of N-cadherin mRNA required an E-box cis-element located within the first intron (+2,627) of the N-cadherin, gene. These data raise the possibility that integrin-mediated adhesion to interstitial matrix proteins during metastasis differentially regulates the nuclear/cytoplasmic translocation and DNA binding of Twist1, activating N-cadherin transcription.