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Article Open Access

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
  • View Affiliations / Copyright

    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
    Copyright: © Nilsson et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 82-94
    |
    Published online on: May 7, 2014
       https://doi.org/10.3892/ijo.2014.2424
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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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Copy and paste a formatted citation
Spandidos Publications style
Nilsson GM, Akhtar N, Kannius-Janson M and Baeckström D: Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition. Int J Oncol 45: 82-94, 2014.
APA
Nilsson, G.M., Akhtar, N., Kannius-Janson, M., & Baeckström, D. (2014). Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition. International Journal of Oncology, 45, 82-94. https://doi.org/10.3892/ijo.2014.2424
MLA
Nilsson, G. M., Akhtar, N., Kannius-Janson, M., Baeckström, D."Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition". International Journal of Oncology 45.1 (2014): 82-94.
Chicago
Nilsson, G. M., Akhtar, N., Kannius-Janson, M., Baeckström, D."Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition". International Journal of Oncology 45, no. 1 (2014): 82-94. https://doi.org/10.3892/ijo.2014.2424
Copy and paste a formatted citation
x
Spandidos Publications style
Nilsson GM, Akhtar N, Kannius-Janson M and Baeckström D: Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition. Int J Oncol 45: 82-94, 2014.
APA
Nilsson, G.M., Akhtar, N., Kannius-Janson, M., & Baeckström, D. (2014). Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition. International Journal of Oncology, 45, 82-94. https://doi.org/10.3892/ijo.2014.2424
MLA
Nilsson, G. M., Akhtar, N., Kannius-Janson, M., Baeckström, D."Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition". International Journal of Oncology 45.1 (2014): 82-94.
Chicago
Nilsson, G. M., Akhtar, N., Kannius-Janson, M., Baeckström, D."Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition". International Journal of Oncology 45, no. 1 (2014): 82-94. https://doi.org/10.3892/ijo.2014.2424
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