APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells

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.