Apical membrane localization of glycogen synthase kinase 3beta protein in normal colon epithelium and aberrant distribution in colorectal cancer

• Published in: Cancer letters Vol. 275; no. 1; pp. 158 - 162
• Main Authors: Hirakawa, Hiroshi, Nakayama, Toshiyuki, Shibata, Kenichiro, Mihara, Yumi, Taba, Mitsuru, Nagayasu, Takeshi, Sekine, Ichiro
• Format: Journal Article
• Language: English
• Published: Ireland 08-03-2009
• Subjects: beta Catenin - metabolism; Cell Membrane - metabolism; Cell Nucleus - metabolism; Colon - enzymology; Colonic Neoplasms - enzymology; Disease Progression; Epithelium - enzymology; Epithelium - metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Models, Biological; Mucin-1 - metabolism; Signal Transduction; Wnt Proteins - metabolism
• ISSN: 1872-7980
• DOI: 10.1016/j.canlet.2008.10.006

Glycogen synthase kinase 3beta (GSK-3beta) was subsequently shown to function in a wide range of cellular processes. GSK-3beta is a multifunctional serine/threonine kinase which performs a role in several signaling pathways including Wnt signal transduction. Recently, the activity of membrane-localized GSK-3beta has been shown to be crucial for initiation of Wnt cascade. In our study, the membrane localization of GSK-3beta was found on the apical membrane of normal epithelium, where co-localized and directly bound with MUC1. In colorectal cancer, depolarized cells showed the aberrant distribution of GSK-3beta on the cellular membrane with beta-catenin nuclear accumulation. The aberrant distribution of the membrane-localized GSK-3beta may contribute to the development of colorectal cancer.