Glycogen synthase kinase 3β (GSK-3β) is a multifunctional serine/threonine kinase involved in several signaling pathways. Recently, we reported the polarized localization of GSK-3β on the apical membrane of normal colon epithelium. To investigate the functions of this molecule, we studied stomach and colorectal cancer tissues. In normal simple columnar epithelium, GSK-3β was localized with tight junction-associated protein ZO-1 in a single line at the apical cell border. GSK-3β and ZO-1 were localized in the apical regions of tubular adenocarcinoma, similar to their localization in normal epithelium; however, their localization was different at the invasive front of the cancer and was found to be associated with lymphatic invasion. In signet-ring cell carcinoma of the stomach, the expression of these proteins was reduced and dot-like expression was observed in each cell of the signet-ring cell carcinoma. We speculated that GSK-3β is involved in glandular structure formation and that the non-apical localization of membrane-localized GSK-3β in tubular adenocarcinoma is associated with cancer development.

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