Interruption of β-catenin suppresses the EGFR pathway by blocking multiple oncogenic targets in human glioma cells

Malignant gliomas are the most common type of intrinsic central nervous system (CNS) tumors with high mortality and morbidity. beta-catenin is overexpressed in human glioblastoma and knockdown of beta-catenin inhibits glioblastoma cell proliferation and invasive ability, and induces apoptotic cell death. Furthermore, treating the nude mice carrying established subcutaneous LN229 gliomas with siRNA targeting beta-catenin intratumorally also delayed the tumor growth. However, the mechanisms of down-regulation of beta-catenin that represses glioblastoma malignancy behavior remain to be elucidated. We utilized text-mining of MEDLINE abstracts with natural language processing to establish the beta-catenin biologic association network, and identified several interactions of this network with the EGFR pathway. In both in vitro and in vivo studies, our results confirmed down-regulation of beta-catenin induced reduced expression of EGFR, STAT3 and AKT1 mRNA and protein, besides, the level of phosphorylated Akt also decreased. A similar reduction in expression of CyclinD1, MMP2 and MMP9, downstream genes of the EGFR pathway, was observed. These results suggest that the Wnt/beta-catenin pathway regulates glioma cell proliferation and invasion, in part via the EGFR pathway. (C) 2010 Elsevier B.V. All rights reserved.