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.