Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Stoffw Microb Lipid

Regulation of Hepatocyte Growth Factor Induced Loss of Adhesion in Melanocyte Cells

Abstract
The intent of this project is to continue our investigations on the importance of hepatocyte
growth factor/scatter factor (HGF/SF) for early events and progression in melanomagenesis.
In the past we had shown that a progressive loss of E-cadherin expression occurs during
melanoma development and HGF/SF downregulates E-cadherin and Desmoglein-1. In this
line of investigations we intend to study the functional regulation of E-cadherin/Desmoglein-
1/Plakoglobulin expression by HGF/SF and the influence of Wnts on HGF induced decrease
in cell-cell adhesion in melanocytes and melanoma cells. Results from these studies will
significantly contribute to our understanding of how skin homeostasis can be dysregulated by
a growth factor, which is thought to be crucial for paracrine stimulation of melanocytes.
Further evidence for the transforming capability of HGF/SF will be provided by alterations in
Wnt expression, a modulator of cell-cell interactions. The following hypothesis - Regulation
of Hepatocyte Growth Factor/Scatter Factor Induced Loss of E-cadherin and
Desmoglein 1 in Melanocytic Cells – will be tested in two specific aims. Specific Aim 1)
study the structural and functional regulation of c-Met induced dissociation of the cadherincatenin
complex through cytoplasmic tyrosine kinases and identify transcription factor(s),
which are possibly involved in epithelial-mesenchymal transition induced by HGF/SF; and
Specific Aim 2) decipher the regulatory effects of Wnts-2, 5a and 7a in HGF/SF induced loss
of cadherin-mediated cell-cell adhesion.
Schlagworte
c-Met
Desmoglein
E-cadherin
Frizzled
Hepatocyte growth factor/Scatter factor
Keratinocyte
Melanocyte
Melanoma
SIP1
Slug
Snail
TCF/LEF
Twist
Wnt
Projektleitung:
Schaider Helmut
Laufzeit:
01.12.2005-31.12.2007
Programm:
FWF Einzelprojekt
Art der Forschung
Grundlagenforschung
Mitarbeiter*innen
Schaider, Helmut, Projektleiter*in
Beteiligte MUG-Organisationseinheiten
Abteilung Zentrum für Medizinische Forschung (ZMF)
Klinische Abteilung für allgemeine Dermatologie (aufgelöst)
Gefördert durch
FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Österreich

FWF-Grant-DOI: 10.55776/P18630
Publizierte Projektergebnisse
> Tight Junction - specific proteins are absent from... J DTSCH DERMATOL GES. 2010; 8(9):750-750.-ADO; Sept 12-14; Hamburg.
> Stage-specific effects of Hepatocyte Growth Factor... J INVEST DERMATOL. JOURNAL OF INVESTIGATIVE DERMATOLOGY2008; 128: S223-S223.-International Investigative Dermatology Meeting; MAY 14-17, 2008; Kyoto, JAPAN.
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