Nuclear expression of Glycogen synthase kinase‐3β and lack of membranous β‐catenin is correlated with poor survival in colon cancer
Open Access
- 7 February 2013
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 133 (4), 807-815
- https://doi.org/10.1002/ijc.28074
Abstract
Dysregulation of Wnt/β-catenin signaling is a hallmark of colon cancer. Glycogen synthase kinase-3β (GSK-3β) can be a positive regulator of survival and proliferation of cultured colon cancer cell but its role in clinical colon cancer is unknown. Our objectives were to evaluate the role of GSK-3β in colon cancer. A tumor tissue microarray of primary colon cancers and metastases was used to evaluate expression and subcellular localization of GSK-3β and β-catenin. In total, 85 primary colon cancer samples were evaluated by immunohistochemistry. Immunoreactivity was correlated to known markers of adverse prognosis. Overall survival was the primary end-point. We found nuclear accumulation of GSK-3β in 39% (33/85) of evaluated tumors. Nuclear GSK-3β was significantly associated with shorter overall survival (p = 0.008), larger tumor size (p = 0.015), distant metastasis (p = 0.029) and loss of membranous β-catenin (p = 0.007). Loss of membranous β-catenin occurred in 37% (30/82) of the tumors and was associated with poor survival (p = 0.016). The combination of nuclear GSK-3β and lack of membrane β-catenin occurred in a total of 26% of the studied tumors (21/61) and was significantly and independently associated with poor prognosis. Our results suggest that nuclear expression of GSK-3β and loss of membrane β-catenin identify a subset of colon carcinomas with worse prognosis.This publication has 26 references indexed in Scilit:
- Dysregulation of Wnt/β-Catenin Signaling in Gastrointestinal CancersGastroenterology, 2012
- A Positive Role of Cadherin in Wnt/β-Catenin Signalling during Epithelial-Mesenchymal TransitionPLOS ONE, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Wnt signaling and colon carcinogenesis: Beyond APCJournal of Carcinogenesis, 2011
- Inhibition of GSK3β enhances both adhesive and signalling activities of β‐catenin in mouse embryonic stem cellsBiology of the Cell, 2010
- Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008International Journal of Cancer, 2010
- Population-Based Family History–Specific Risks for Colorectal Cancer: A Constellation ApproachGastroenterology, 2010
- Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancerEuropean Journal of Cancer, 2010
- Aberrant Nuclear Accumulation of Glycogen Synthase Kinase-3β in Human Pancreatic Cancer: Association with Kinase Activity and Tumor DedifferentiationClinical Cancer Research, 2006
- Deregulated GSK3β activity in colorectal cancer: Its association with tumor cell survival and proliferationBiochemical and Biophysical Research Communications, 2005