Hsp90α/β associates with the GSK3β/axin1/phospho-β-catenin complex in the human MCF-7 epithelial breast cancer model

• Published in: Biochemical and biophysical research communications Vol. 413; no. 4; pp. 550 - 554
• Main Authors: Cooper, Leanne C., Prinsloo, Earl, Edkins, Adrienne L., Blatch, Gregory L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.10.2011
• Subjects: Axin Protein - metabolism; Axin1; beta Catenin - metabolism; Breast cancer; Breast Neoplasms - metabolism; Carcinoma - metabolism; Cell Line, Tumor; Epithelial Cells - metabolism; Female; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; GSK3β; Hsp90; HSP90 Heat-Shock Proteins - metabolism; Humans; Immunoprecipitation; Models, Biological; Phosphorylation; β-Catenin; Hsp90; GSK3β; Axin1; β-Catenin; Breast cancer; Hsp90α/β
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.08.136

► Phosphorylation and degradation of β-catenin regulates Wnt/β-catenin signalling. ► Hsp90α/β chaperones cell signalling. ► Hsp90α/β co-localises with GSK3β, β-catenin and phospho-β-catenin. ► Hsp90α/β immunoprecipitates with phospho-β-catenin and axin1. ► This is the first report of phospho-β-catenin and axin1 as Hsp90α/β client proteins. Hsp90α/β, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90α/β with its client kinases form the framework of multiple signalling networks. GSK3β, a known Hsp90α/β client, mediates β-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-β-catenin to the 26S proteasome. The canonical Wnt/β-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90α/β involvement in Wnt/β-catenin signalling needs clarification. Here, we describe the association of Hsp90α/β with GSK3β, β-catenin, phospho-β-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90α/β, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90α/β modulates the phosphorylation of β-catenin by interaction in common complex with GSK3β/axin1/β-catenin.