Distinct dedifferentiation processes affect caveolin-1 expression in hepatocytes. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Cell Communication and Signaling Year : 2013

Distinct dedifferentiation processes affect caveolin-1 expression in hepatocytes.

Christoph Meyer
  • Function : Author
  • PersonId : 937779
Johanna Dzieran
  • Function : Author
  • PersonId : 937780
Felizitas Schindler
  • Function : Author
  • PersonId : 937782
Stefan Munker
  • Function : Author
  • PersonId : 937783
Alexandra Müller
  • Function : Author
  • PersonId : 937784
Cédric Coulouarn
  • Function : Author
  • PersonId : 945894

Abstract

ABSTRACT: BACKGROUND: Dedifferentiation and loss of hepatocyte polarity during primary culture of hepatocytes are major drawbacks for metabolic analyses. As a prominent profibrotic cytokine and potent inducer of epithelial mesenchymal transition (EMT), TGF-beta contributes to these processes in liver epithelial cells. Yet, a distinction between culture dependent and TGF-beta driven hepatocyte dedifferentiation has not been shown to date. RESULTS: Here, we show that in both settings, mesenchymal markers are induced. However, upregulation of Snai1 and downregulation of E-Cadherin are restricted to TGF-beta effects, neglecting a full EMT of culture dependent hepatocyte dedifferentiation. Mechanistically, the latter is mediated via FAK/Src/ERK/AKT pathways leading to the induction of the oncogene caveolin-1 (Cav1). Cav1 was recently proposed as a new EMT marker, but our results demonstrate Cav1 is not up-regulated in TGF-beta mediated hepatocyte EMT, thus limiting validity of its use for this purpose. Importantly, marking differences on Cav1 expression exist in HCC cell lines. Whereas well differentiated HCC cell lines exhibit low and inducible Cav1 protein levels - by TGF-beta in a FAK/Src dependent manner, poorly differentiated cell lines display high Cav1 expression levels which are not further modulated by TGF-beta. CONCLUSIONS: This study draws a detailed distinction between intrinsic and TGF-beta mediated hepatocyte dedifferentiation and elucidates cellular pathways involved. Additionally, by evaluating the regulation of the oncogene Cav1, we provide evidence to argue against Cav1 as a reliable EMT marker.
Fichier principal
Vignette du fichier
1478-811X-11-6.pdf (584.81 Ko) Télécharger le fichier
1478-811X-11-6.xml (60.57 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Loading...

Dates and versions

inserm-00798003 , version 1 (07-03-2013)

Identifiers

Cite

Christoph Meyer, Johanna Dzieran, Yan Liu, Felizitas Schindler, Stefan Munker, et al.. Distinct dedifferentiation processes affect caveolin-1 expression in hepatocytes.. Cell Communication and Signaling, 2013, 11 (1), pp.6. ⟨10.1186/1478-811X-11-6⟩. ⟨inserm-00798003⟩
391 View
232 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More