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Updated: Jun 21, 2026
Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
Published on: September 15, 2023
Association of cellular localization of glycogen synthase kinase 3beta in the digestive tract with cancer development
Hiroshi Hirakawa1, Toshiyuki Nakayama, Kenichiro Shibata
1Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. h-hira@nagasaki-u.ac.jpc
Abstract:
Glycogen synthase kinase 3beta (GSK-3beta) is a multifunctional serine/threonine kinase involved in several signaling pathways. Recently, we reported the polarized localization of GSK-3beta 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-3beta was localized with tight junction-associated protein ZO-1 in a single line at the apical cell border. GSK-3beta 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-3beta is involved in glandular structure formation and that the non-apical localization of membrane-localized GSK-3beta in tubular adenocarcinoma is associated with cancer development.
Insights
Glycogen synthase kinase 3beta (GSK-3beta) is crucial for normal colon epithelium structure. Its altered localization in cancer tissues suggests a role in tumor development and lymphatic invasion.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Glycogen synthase kinase 3beta (GSK-3beta) is a key kinase in cellular signaling pathways.
- Previous research identified polarized apical membrane localization of GSK-3beta in normal colon epithelium.
Purpose of the Study:
- To investigate the role and localization of GSK-3beta in stomach and colorectal cancer.
- To understand the association of GSK-3beta localization with cancer development and invasion.
Main Methods:
- Immunohistochemical analysis of GSK-3beta and ZO-1 expression in normal, tubular adenocarcinoma, and signet-ring cell carcinoma tissues.
- Comparative analysis of protein localization patterns between normal and cancerous tissues.
Main Results:
- GSK-3beta and ZO-1 showed similar apical localization in normal epithelium and tubular adenocarcinoma.
- Altered GSK-3beta and ZO-1 localization at the invasive front of tubular adenocarcinoma correlated with lymphatic invasion.
- Signet-ring cell carcinoma exhibited reduced expression and dot-like GSK-3beta localization.
Conclusions:
- GSK-3beta is implicated in glandular structure formation.
- Aberrant, non-apical GSK-3beta localization in tubular adenocarcinoma is associated with cancer progression.
- GSK-3beta's altered localization may serve as a biomarker for cancer invasiveness.
