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Göteborgs universitets publikationer

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

Författare och institution:
Gisela M A Nilsson (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi & Institutionen för kemi och molekylärbiologi); Noreen Akhtar (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Marie Kannius-Janson (Institutionen för kemi och molekylärbiologi); Dan Baeckström (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi)
Publicerad i:
International journal of oncology, 45 ( 1 ) s. 82-94
Artikel, refereegranskad vetenskaplig
Sammanfattning (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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Biologiska vetenskaper
Medicinska grundvetenskaper
E-cadherin, EMT
Postens nummer:
Posten skapad:
2014-05-22 14:54
Posten ändrad:
2014-07-03 12:18

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