PCDH24-induced contact inhibition involves downregulation of β-catenin signaling

Elevated expression of the protocadherin LKC (PCDH24) in HCT116 colon carcinoma cells has been shown to induce contact inhibition, thereby completely abolishing tumor formation in vivo (Carcinogenesis, 2002; 23(7):1139–1148). To clarify the molecular mechanism behind this effect, we performed 2-DE/MS and DNA microarray analyses in order to compare protein and gene expression patterns of parental HCT116 and PCDH24-expressing HTC116 derivative cells. The data revealed drastic changes in phenotypic markers between parental and PCDH24-expressing cells. We found that in PCDH24-expressing cells β-catenin, a major player in TCF/lef signaling, is retained in a submembranous location. β-catenin retention coincided with a subsequent decrease in downstream targets of β-catenin such as CD44, PLAUR, Myc, cyclin D1 and Met. From these findings we propose a novel model for the suppression of β-catenin signaling by PCDH24 that leads to contact inhibition.