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2015 ; 4
(6
): e157
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An aberrant nuclear localization of E-cadherin is a potent inhibitor of
Wnt/?-catenin-elicited promotion of the cancer stem cell phenotype
#MMPMID26075748
Su YJ
; Chang YW
; Lin WH
; Liang CL
; Lee JL
Oncogenesis
2015[Jun]; 4
(6
): e157
PMID26075748
show ga
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-cadherin(Low)/nuclear ?-catenin(High)/CD133(High) biomarkers has superior
prognostic value over total E-cadherin(Low)/nuclear ?-catenin(High)/CD133(High).