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SHR Neuro Cancer Cardio Metab 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.

Keywords: c-Met; Desmoglein; E-cadherin; Frizzled; Hepatocyte growth factor/Scatter factor; Keratinocyte; Melanocyte; Melanoma; SIP1; Slug; Snail; TCF/LEF; Twist; Wnt

Project Leader:: Schaider Helmut

Duration:: 01.12.2005-31.12.2007

Programme:: Einzelprojekt

Type of Research: basic research

Staff: Schaider, Helmut, Project Leader

MUG Research Units: Center for Medical Research (ZMF); Division of General Dermatology (closed)

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > 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.