TY - JOUR
T1 - Autoregulation of E-cadherin expression by cadherin-cadherin interactions
T2 - The roles of β-catenin signaling, Slug, and MAPK
AU - Conacci-Sorrell, Maralice
AU - Simcha, Inbal
AU - Ben-Yedidia, Tamar
AU - Blechman, Janna
AU - Savagner, Pierre
AU - Ben-Ze'Ev, Avri
PY - 2003/11/24
Y1 - 2003/11/24
N2 - Transcriptional repression of E-cadherin, characteristic of epithelial to mesenchymal transition, is often found also during tumor cell invasion. At metastases, migratory fibroblasts sometimes revert to an epithelial phenotype, by a process involving regulation of the E-cadherin-β-catenin complex. We investigated the molecular basis of this regulation, using human colon cancer cells with aberrantly activated β-catenin signaling. Sparse cultures mimicked invasive tumor cells, displaying low levels of E-cadherin due to transcriptional repression of E-cadherin by Slug. Slug was induced by β-catenin signaling and, independently, by ERK. Dense cultures resembled a differentiated epithelium with high levels of E-cadherin and β-catenin in adherens junctions. In such cells, β-catenin signaling, ErbB-1/2 levels, and ERK activation were reduced and Slug was undetectable. Disruption of E-cadherin-mediated contacts resulted in nuclear localization and signaling by β-catenin, induction of Slug and inhibition of E-cadherin transcription, without changes in ErbB-1/2 and ERK activation. This autoregulation of E-cadherin by cell-cell adhesion involving Slug, β-catenin and ERK could be important in tumorigenesis.
AB - Transcriptional repression of E-cadherin, characteristic of epithelial to mesenchymal transition, is often found also during tumor cell invasion. At metastases, migratory fibroblasts sometimes revert to an epithelial phenotype, by a process involving regulation of the E-cadherin-β-catenin complex. We investigated the molecular basis of this regulation, using human colon cancer cells with aberrantly activated β-catenin signaling. Sparse cultures mimicked invasive tumor cells, displaying low levels of E-cadherin due to transcriptional repression of E-cadherin by Slug. Slug was induced by β-catenin signaling and, independently, by ERK. Dense cultures resembled a differentiated epithelium with high levels of E-cadherin and β-catenin in adherens junctions. In such cells, β-catenin signaling, ErbB-1/2 levels, and ERK activation were reduced and Slug was undetectable. Disruption of E-cadherin-mediated contacts resulted in nuclear localization and signaling by β-catenin, induction of Slug and inhibition of E-cadherin transcription, without changes in ErbB-1/2 and ERK activation. This autoregulation of E-cadherin by cell-cell adhesion involving Slug, β-catenin and ERK could be important in tumorigenesis.
KW - Cell adhesion
KW - ERK
KW - Slug
KW - Tumorigenesis
KW - β-catenin
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U2 - 10.1083/jcb.200308162
DO - 10.1083/jcb.200308162
M3 - Article
C2 - 14623871
AN - SCOPUS:0345599013
SN - 0021-9525
VL - 163
SP - 847
EP - 857
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -