The APC tumor suppressor protein is associated with the regulation of Wnt signaling, however APC also controls other cellular processes including the regulation of cell adhesion and migration. The expression of full-length APC in SW480 colorectal cancer cells (SW480+APC) not only reduces Wnt signaling, but increases membrane E-cadherin and restores cell-cell adhesion. This report describes the effects of full-length, wild-type APC (fl-APC) on cell-cell adhesion genes and p120-catenin isoform switching in SW480 colon cancer cells: fl-APC increased the expression of genes implicated in cell-cell adhesion, whereas the expression of negative regulators of E-cadherin were decreased. Analysis of cell-cell adhesion-related proteins in SW480+APC cells revealed an increase in p120-catenin isoform 3A; similarly, depletion of APC altered the p120-catenin protein isoform profile. Expression of ESRP1 (epithelial splice regulatory protein 1) is increased in SW480+APC cells and its depletion results in reversion to the p120-catenin isoform 1A phenotype and reduced cell-cell adhesion. ESRP1 transcript is reduced in primary CRC and its expression correlates with the level of APC. Pyrvinium pamoate, which inhibits Wnt signaling, promotes ESRP1 expression. We conclude that re-expression of APC restores cell-cell adhesion gene and post-transcriptional regulatory programs leading to p120-catenin isoform switching and associated changes in cell-cell adhesion.

在APC肿瘤抑制蛋白与Wnt信号传导的调节相关，但APC还控制其他细胞过程，包括细胞粘附和迁移的调节。全长的APC在SW480结直肠癌细胞中的表达（SW480 + APC）不仅降低了Wnt信号传导，但增加膜E-钙粘蛋白和恢复细胞 - 细胞粘附。本报告描述全长，野生型APC（FL-APC）对细胞 - 细胞粘附的基因和在SW480结肠癌细胞P120连环蛋白同种型转换的效应：FL-APC增加细胞 - 细胞有关的基因的表达附着力，而E-钙粘蛋白的负调节的表达明显降低。在SW480 + APC细胞的细胞 - 细胞粘着相关的蛋白质的分析表明，在P120连环蛋白同种型3A的增加; 相似地，APC枯竭改变了P120-catenin蛋白异构体的轮廓。ESRP1（上皮剪接调控蛋白1）的表达在SW480 + APC细胞及其消耗导致逆转增大到P120连环蛋白同种型的表型1A和降低的细胞 - 细胞粘附。ESRP1 转录本在原发性 CRC 中减少，其表达与 APC 水平相关。Pyrvinium双羟萘酸盐，其抑制Wnt信号传导，促进ESRP1表达。我们得出结论，导致P120连环蛋白亚型交换和细胞间黏附相关的变化APC恢复细胞 - 细胞粘附基因和转录后调控计划署的再表达。ESRP1（上皮剪接调控蛋白1）的表达在SW480 + APC细胞及其消耗导致逆转增大到P120连环蛋白同种型的表型1A和降低的细胞 - 细胞粘附。ESRP1转录物在初级CRC及其表达相关与APC的水平降低。Pyrvinium双羟萘酸盐，其抑制Wnt信号传导，促进ESRP1表达。我们得出结论，APC 的重新表达恢复了细胞 - 细胞粘附基因和转录后调节程序，导致 p120-连环蛋白同种型转换和细胞 - 细胞粘附的相关变化。ESRP1（上皮剪接调控蛋白1）的表达在SW480 + APC细胞及其消耗导致逆转增大到P120连环蛋白同种型的表型1A和降低的细胞 - 细胞粘附。ESRP1转录物在初级CRC及其表达相关与APC的水平降低。Pyrvinium双羟萘酸盐，其抑制Wnt信号传导，促进ESRP1表达。我们得出结论，导致P120连环蛋白亚型交换和细胞间黏附相关的变化APC恢复细胞 - 细胞粘附基因和转录后调控计划署的再表达。