“Molecular mechanisms of proteolytically- activated oncogenes in epithelial tumors”
We focus on studying the molecular mechanisms of epithelial tumor growth, invasion/dissemination and metastasis. Under the influence of extracellualr matrix (ECM), normal epithelial cells form highly organized and polarized cell layers. Attachment to the ECM is required for the control of normal cell proliferation, differentiation and survival. In-contrast, during cancer progression normal cell architecture and morphogenesis are disrupted and the malignant cells proliferate and survive outside their normal niches. This process is recapitulated in three-dimensional cell cultures in vitro as also in vivo in appropriate mouse xenograft models. In this context, we particularly investigate the involvement of mammalian protease-activated-receptors (PARs) family which are activated by proteases found in the flexible microenvironment of a tumor and play a central role in epithelial carcinoma. Our approach engages invariably the study of gene over-expression, promoter analyses, tissue microarray evaluation, cell-signaling as also appropriate mouse models.
1. The molecular mechanism of protease-activated-receptor (PAR) family in epithelial malignancies
2. Translational research: Identification of novel target - domains for therapy
3. Mammalian PAR signaling: Involvement of b-catenin pathway and impact on tumor growth
4. Transcriptional regulation: Promoter analyses of PAR1 and PAR2
|A PAR1 mutant abrogating Etk/BMX binding inhibits the generation of PAR1 induced mammary gland tumors
||Cohen I et al PLoS ONE, 2010|
|PAR1 expression in breast cancer tissue micro-array
||Salah Z et al., FASEB J, 2012|
Available PositionsPhD students and Post Doc
Excellent motivated students with a good background in cell biology are welcome to join us. While the projects involve basic biology research it is intimately associated with clinical aspects and close collaboration with skilled physicians.