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Background
The APC tumour suppressor functions in several cellular processes including the regulation of β-catenin in Wnt signalling and in cell adhesion and migration.Findings
In this study, we establish that in epithelial cells N-terminally phosphorylated β-catenin specifically localises to several subcellular sites including cell-cell contacts and the ends of cell protrusions. N-terminally phosphorylated β-catenin associates with E-cadherin at adherens junctions and with APC in cell protrusions. We isolated APC-rich protrusions from stimulated cells and detected β-catenin, GSK3β and CK1α, but not axin. The APC/phospho-β-catenin complex in cell protrusions appears to be distinct from the APC/axin/β-catenin destruction complex. GSK3β phosphorylates the APC-associated population of β-catenin, but not the cell junction population. β-catenin associated with APC is rapidly phosphorylated and dephosphorylated. HGF and wound-induced cell migration promote the localised accumulation of APC and phosphorylated β-catenin at the leading edge of migrating cells. APC siRNA and analysis of colon cancer cell lines show that functional APC is required for localised phospho-β-catenin accumulation in cell protrusions.Conclusions
We conclude that N-terminal phosphorylation of β-catenin does not necessarily lead to its degradation but instead marks distinct functions, such as cell migration and/or adhesion processes. Localised regulation of APC-phospho-β-catenin complexes may contribute to the tumour suppressor activity of APC. 相似文献5.
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Hui Pang Hailing Lu Hongtao Song Qingwei Meng Yanbin Zhao Na Liu Fei Lan Ying Liu Suhong Yan Xiaoqun Dong Li Cai 《Cancer epidemiology》2013,37(6):985-992
ObjectiveTo determine the correlation of cell adhesion molecules (osteopontin-c, E-cadherin and β-catenin) with clinicopathological characteristics in breast cancer.MethodsImmunostaining of osteopontin-c, E-cadherin and β-catenin were conducted in 170 samples of breast cancer and 30 samples of adjacent normal breast tissues. The correlation of osteopontin-c, E-cadherin and β-catenin expression level with clinicopathological characteristics was evaluated by Pearson's chi-square and Wilcoxon rank-sum test. Univariate and multivariate Cox hazard regression model was used to assess the prognostic values of osteopontin-c, E-cadherin and β-catenin in clinical outcome of breast cancer.ResultsA higher level of osteopontin-c whereas lower levels of E-cadherin and β-catenin were observed in breast cancer as compared with the normal breast tissues. The expression of osteopontin-c was negatively associated with the expression of E-cadherin and β-catenin. The expression of osteopontin-c correlated with lymph node metastasis, and advanced TNM stage and histologic grade. The expression of E-cadherin correlated with low histologic grade; and β-catenin with low TNM stage and histological grade. Moreover, high osteopontin-c level correlated with tumor recurrence or metastasis as well as triple negative subtype. The expression of osteopontin-c was an independent prognostic factor for both disease-free and overall survival of breast cancer patients.ConclusionThe data suggest that the expression of osteopontin-c could serve as a prognostic factor of breast cancer. 相似文献
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