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Curr Chem Genomics. 2012;6:18-26. doi: 10.2174/1875397301206010018. Epub 2012 Sep 20.

Galectin-1 and Galectin-3 Mediate Protocadherin-24-Dependent Membrane Localization of β-catenin in Colon Cancer Cell Line HCT116.

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  • 1Department 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.

Abstract

Protocadherin-24 (PCDH24) is linked to the suppression of tumor growth and the inhibition of cell proliferation in the colon cancer cell line HCT116. We previously observed that β-catenin is localized to the plasma membrane when PCDH24 is expressed in these cells, but the molecular mechanisms by which PCDH24 induces the membrane localization of β-catenin remain largely unknown. To clarify these mechanisms, we identified molecules that interact with ectopically expressed PCDH24 in HCT116 cells using a HaloTag® pull-down assay. We found that galectin-1 and galectin-3 physically interact with PCDH24 and are retained at the plasma membrane in association with PCDH24 expression. A luciferase-based pull-down assay using HaloTag-fused galectins revealed that an intracellular region of PCDH24 (amino acids 1186-1280) is essential for this interaction. Furthermore, the over-expression of galectin-1 or -3, or the depletion of endogenous galectins by small interfering RNA modulates β-catenin translocation. We also revealed that the retention of galectin-1 and -3 at the plasma membrane results in the inactivation of PI3K activity. From these findings, we propose a model in which the galectin-anchoring activity of PCDH24 leads to the suppression of β-catenin signaling by the localization of β-catenin at the plasma membrane in PCDH24-expressing HCT116 colon cancer cells.

KEYWORDS:

HCT116; HaloTag; PCDH24; galectin-1; galectin-3; pull-down assay.; β-catenin

PMID:
23115611
[PubMed]
PMCID:
PMC3480823
Free PMC Article
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