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

Ose, Rui; Yanagawa, Toshihide; Ikeda, Shun; Ohara, Osamu; Koga, Hisashi

doi:10.1016/j.molonc.2008.10.005

« Previous Next »Molecular Oncology
Volume 3, Issue 1 , Pages 54-66, February 2009

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

Rui Ose
- Laboratory of Medical Genomics, Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan
- Graduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan
Toshihide Yanagawa
- Laboratory of Medical Genomics, Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan
Shun Ikeda
- Laboratory of Medical Genomics, Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan
Osamu Ohara
- Graduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan
- Laboratory of Genome Technology, Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan
- Laboratory for Immunogenomics, Research Center for Allergy and Immunology, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Hisashi Koga
- Laboratory of Medical Genomics, Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan
- Corresponding author. Tel.: +81 438 52 3505; fax: +81 438 52 3914.

Received 4 August 2008; received in revised form 14 October 2008; accepted 28 October 2008. published online 28 November 2008.

Abstract

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.

Keywords: PCDH24, Contact inhibition, β-catenin, HCT116, Actin, Vimentin

Abbreviations: qRT-PCR, quantitative real-time-PCR, LMB, leptomycin B, 2-DE/MS, two-dimensional gel electrophoresis/mass spectrometry, PLAUR, plasminogen activator urokinase receptor