Hsp90 alpha/beta, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90 alpha/beta with its client kinases form the framework of multiple signalling networks. GSK3 beta, a known Hsp90 alpha/beta client, mediates beta-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-beta-catenin to the 26S proteasome. The canonical Wnt/beta-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90 alpha/beta involvement in Wnt/beta-catenin signalling needs clarification. Here, we describe the association of Hsp90 alpha/beta with GSK3 beta, beta-catenin, phospho-beta-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90 alpha/beta, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90 alpha/beta modulates the phosphorylation of beta-catenin by interaction in common complex with GSK3 beta/axin1/beta-catenin. (C) 201 1 Elsevier Inc. All rights reserved.