Autoregulation of E-cadherin expression by cadherin-cadherin interactions

The roles of β-catenin signaling, Slug, and MAPK

Maralice Conacci-Sorrell, Inbal Simcha, Tamar Ben-Yedidia, Janna Blechman, Pierre Savagner, Avri Ben-Ze'Ev

Research output: Contribution to journalArticle

351 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)847-857
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number4
DOIs
StatePublished - Nov 24 2003

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Catenins
Gastropoda
Cadherins
Homeostasis
Adherens Junctions
Epithelial-Mesenchymal Transition
Cell Adhesion
Colonic Neoplasms
Neoplasms
Carcinogenesis
Epithelium
Fibroblasts
Neoplasm Metastasis
Phenotype

Keywords

  • β-catenin
  • Cell adhesion
  • ERK
  • Slug
  • Tumorigenesis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Autoregulation of E-cadherin expression by cadherin-cadherin interactions : The roles of β-catenin signaling, Slug, and MAPK. / Conacci-Sorrell, Maralice; Simcha, Inbal; Ben-Yedidia, Tamar; Blechman, Janna; Savagner, Pierre; Ben-Ze'Ev, Avri.

In: Journal of Cell Biology, Vol. 163, No. 4, 24.11.2003, p. 847-857.

Research output: Contribution to journalArticle

Conacci-Sorrell, Maralice ; Simcha, Inbal ; Ben-Yedidia, Tamar ; Blechman, Janna ; Savagner, Pierre ; Ben-Ze'Ev, Avri. / Autoregulation of E-cadherin expression by cadherin-cadherin interactions : The roles of β-catenin signaling, Slug, and MAPK. In: Journal of Cell Biology. 2003 ; Vol. 163, No. 4. pp. 847-857.
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