Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition

Nilsson,Gisela M.A.; Akhtar,Noreen; Kannius-Janson,Marie; Baeckström,Dan

doi:10.3892/ijo.2014.2424

Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition

Authors:
- Gisela M.A. Nilsson
- Noreen Akhtar
- Marie Kannius-Janson
- Dan Baeckström
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Affiliations: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden, Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Published online on: May 7, 2014 https://doi.org/10.3892/ijo.2014.2424
Pages: 82-94
Copyright: © Nilsson et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Recent research into the mechanisms of tumour cell invasiveness has highlighted the parallels between carcinogenesis and epithelial-mesenchymal transition (EMT), originally described as a developmental transdifferentiation program but also implicated in fibrosis and cancer. In a model system for mammary carcinogenesis, we previously observed that induced signalling from a homodimer of the c-erbB2 (HER2) receptor tyrosine kinase in an initially non-malignant mammary cell line caused EMT where i) cell scattering occurred before downregulation of the cell-cell adhesion molecule E-cadherin and ii) the progress of EMT was dramatically delayed when cells were grown at high density. Here, we have further analysed these phenomena. Ectopic expression of E-cadherin concomitant with c-erbB2 signalling was unable to impede the progression of EMT, suggesting that E-cadherin downregulation is not required for EMT. Furthermore, fibroblast-like cells isolated after EMT induced in the presence or absence of ectopic E-cadherin expression showed highly similar morphology and vimentin expression. E-cadherin expressed in these fibroblastic cells had a subcellular localisation similar to that found in epithelial cells, but it exhibited a much weaker attachment to the cytoskeleton, suggesting cytoskeletal rearrangements as an important mechanism in EMT-associated cell scattering. We also investigated whether density-dependent inhibition of EMT is mediated by E-cadherin as a sensor for cell-cell contact, by expressing dominant-negative E-cadherin. While expression of this mutant weakened cell-cell adhesion, it failed to facilitate EMT at high cell densities. These results indicate that loss of E-cadherin expression is a consequence rather than a cause of c-erbB2-induced EMT and that density‑dependent inhibition of EMT is not mediated by E-cadherin signalling.

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