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Determining the Hierarchy of EMTRs in Malignant Melanoma

Abstract
Epithelial-mesenchymal transition (EMT) is a hallmark of cellular transformation in solid tumors. A similar process is thought to be relevant for melanomgenesis. The exact mechanisms how this is accomplished with respect to stage specific effects of epilthelial-mesenchymal transcriptional regulation, however, are unknown for many tumor entities and melanoma in particular.
The intent of this project is to decipher targets of EMT inducing regulators at the transcriptional level as exemplified by modulation of cadherins through hepatocyte growth factor (HGF), an important growth factor in melanomagenesis. Our previous data show that the effect of HGF on epithelial-mesenchymal transcriptional regulators (EMTRs) is stage-dependent in melanoma cell lines. Based on these observations we want to pinpoint EMTRs specific binding to E-boxes in cadherins, investigate on HGF-mediated regulation of Snail and Slug and study overexpression of Slug and Twist in melanoma cell lines. We expect to uncover the hierachical sequence of EMTRs activation in early versus late stage melanomas, the preferential binding of EMRTs to cadherins and in vitro and in vivo effects of over-expressed or down-regulated EMRTs. The following hypothesis:
"Hierachy of epithelial-mesenchymal transcriptional regulators in malignant melanoma"
will be tested in two specific aims:
*Continuing investigations on E-box binding EMRTs and the functional effects of Slug and Twist in melanocytic cells
*Scrutinizing HGF mediated modulation of Snail, Slug and Twist through regulation by NF-kB and GSK -3ß.
Keywords
cancer research
skin and venereal disease
Project Leader:
Schaider Helmut
Duration:
15.01.2009-14.01.2011
Programme:
Einzelprojekt
Type of Research
other
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

FWF-Grant-DOI: 10.55776/P21156
Project results published
> Naphthoquinones from Onosma paniculata induce cell... J Nat Prod. 2012; 75(5):865-869
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