An aberrant nuclear localization of E-cadherin is a potent inhibitor of Wnt/beta-catenin-elicited promotion of the cancer stem cell phenotype

作者：Su Y J; Chang Y W; Lin W H; Liang C L; Lee J L^*

来源：Oncogenesis, 2015, 4(6): e157.

DOI：10.1038/oncsis.2015.17

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/beta-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 beta-catenin in gastric and colorectal carcinomas. Here we conducted a series of in-vitro and in-vivo studies to show that the beta-catenin/TCF4 interaction was abolished by E-cadherin and was correlated with its nuclear localization, and consequently decreased beta-catenin/TCF4 transcriptional activity. Nuclear E-cadherin was a negative regulator of Wnt/beta-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 beta-catenin(High)/CD133(High) biomarkers has superior prognostic value over total E-cadherinLow/nuclear beta-catenin(High)/CD133(High).

• 出版日期2015-6
• 单位清华大学