Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Int J Oncol. 2010 Oct;37(4):909-26. doi: 10.3892/ijo_00000742.
Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions. The acquisition of the EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of this pathway by U0126 treatment in E1 cells resulted in the re-expression of palladin, relocalization of E-cadherin to the adherens junctions and a reversal of EMT features. The re-establishment of intercellular adhesion was dependent on palladin expression. The down-regulation of palladin was also observed in poorly-differentiated tumor tubules and dissociated tumor cells that have undergone de-differentiation in human primary colon tumors. Our data show that palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma.
帕拉丁（Palladin）是一种支架蛋白，参与肌动蛋白相关蛋白复合物的形成。对低转移性 HCT116 结肠癌细胞系和具有 EMT（上皮-间充质转化）特征的转移性衍生细胞系（E1）进行基因表达谱分析显示，后者中帕拉丁基因表达下调。在 HCT116 细胞中敲低帕拉丁表达会抑制 E-钙黏蛋白的连接定位，减少细胞间黏附性和细胞集体迁移，表明帕拉丁在维持黏附连接的完整性方面发挥着重要作用。E1 细胞系获得 EMT 特征依赖于 Erk 通路。在 E1 细胞中用 U0126 处理抑制该通路会导致帕拉丁重新表达，E-钙黏蛋白重新定位到黏附连接，并逆转 EMT 特征。细胞间黏附的重建依赖于帕拉丁的表达。在人类原发性结肠肿瘤中，低分化肿瘤小管和已经去分化的分离肿瘤细胞中也观察到帕拉丁的下调。我们的数据表明，帕拉丁是黏附连接的组成部分，在 E-钙黏蛋白定位到连接中发挥作用。帕拉丁的丢失可能是 EMT 的一个组成部分，是结肠癌细胞转移扩散的早期步骤。
