https://scholars.lib.ntu.edu.tw/handle/123456789/391092
標題: | An aberrant nuclear localization of E-cadherin is a potent inhibitor of Wnt/β-catenin-elicited promotion of the cancer stem cell phenotype. | 作者: | WEI-HSIN LIN Chang Y.-W. Liang C.-L. Lee J.-L. |
公開日期: | 2015 | 摘要: | Several studies suggest that Wnt signaling contributes to reprogramming and maintenance of cancer stem cell (CSC) states activated by loss of membranous E-cadherin expression. However, E-cadherin's exact role in Wnt/?-catenin-mediated promotion of the CSC phenotype remains unclear. Recently, a significant positive correlation has been observed between the expression of nuclear (an aberrant nuclear localization) E-cadherin and ?-catenin in gastric and colorectal carcinomas. Here we conducted a series of in-vitro and in-vivo studies to show that the ?-catenin/TCF4 interaction was abolished by E-cadherin and was correlated with its nuclear localization, and consequently decreased ?-catenin/TCF4 transcriptional activity. Nuclear E-cadherin was a negative regulator of Wnt/?-Catenin-elicited promotion of the CSC phenotype. Using immunohistochemistry on lung cancer tissue microarrays, we found that changes in subcellular location of E-cadherin may be described by tumor grade and stage, suggesting cellular redistribution during lung tumorigenesis. Furthermore, nuclear E-cadherin expression was more significantly inversely correlated with CD133 (a lung CSC marker) expression (P<0.005) than total E-cadherin expression (P<0.05), suggesting that lung cancer as defined by nuclear E-cadherinLow/nuclear ?-cateninHigh/CD133High biomarkers has superior prognostic value over total E-cadherinLow/nuclear ?-cateninHigh/CD133High. |
URI: | http://europepmc.org/abstract/med/26075748 http://scholars.lib.ntu.edu.tw/handle/123456789/391092 |
DOI: | 10.1038/oncsis.2015.17 | SDG/關鍵字: | ABC transporter; beta catenin; breast cancer resistance protein; CD133 antigen; protein; short hairpin RNA; TCF4 protein; unclassified drug; uvomorulin; Wnt protein; animal experiment; animal model; Article; binding site; cancer stem cell; carcinogenicity; cell clone; cell fractionation; cell proliferation assay; cell stimulation; confocal microscopy; controlled study; ectopic expression; endocytosis; female; flow cytometry; human; human cell; human tissue; immunohistochemistry; immunoprecipitation; in vitro study; in vivo study; internalization; lung cancer; nonhuman; overall survival; phenotype; priority journal; promoter region; protein degradation; protein expression; protein localization; protein phosphorylation; protein protein interaction; supernatant; tissue microarray; transcription initiation; Western blotting; Wnt signaling pathway |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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