WEI-HSIN LINChang Y.-W.Liang C.-L.Lee J.-L.2018-09-102018-09-102015http://europepmc.org/abstract/med/26075748http://scholars.lib.ntu.edu.tw/handle/123456789/391092Several 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.[SDGs]SDG3ABC 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 pathwayjournal article10.1038/oncsis.2015.17