PCDH24-induced contact inhibition involves downregulation of beta-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 beta-catenin, a major player in TCF/lef signaling, is retained in a submembranous location. beta-catenin retention coincided with a subsequent decrease in downstream targets of beta-catenin such as CD44, PLAUR, Myc, cyclin D1 and Met. From these findings we propose a novel model for the suppression of beta-catenin signaling by PCDH24 that leads to contact inhibition.
Ose
Rui
R
Laboratory of Medical Genomics, Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan.
Yanagawa
Toshihide
T
Ikeda
Shun
S
Ohara
Osamu
O
Koga
Hisashi
H
D015415:Biomarkers; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D003260:Contact Inhibition; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D040901:Proteomics; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
D015415:Biomarkers; C464586:CDHR2 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D051176:beta Catenin