Regulation of cell proliferation in cancer
Understanding how signal transduction is controlled is an important issue in biology with huge implications for understanding cancer.
The strictly coordinated cellular response to external signal is critical for many malignant cellular features including unrestricted and/or anchorage independent growth, increased disposition to migrate, as well as decreased adherence.
Consequently, many of the alterations found in cancer perturb molecular signaling and thereby cause a strongly reduced dependence on external mitogenic stimulation.
Most of our current projects are designed in order to clarify the role of Sprouty proteins in cell signaling and cancer. Thereby, one part of our investigations aims to elucidate the molecular basis of Sprouty functions as inhibitors of RTK-mediated processes like cell proliferation and migration.
These analyses investigate which kind of processes the Sprouty proteins interfere with, what are the proteins they interact with, what are the pathways they influence, and what is their potential to be used as an endogenous inhibitor of cell proliferation.
To assess the functions of Sprouty proteins as antagonists of receptor tyrosine kinases (RTKs) in tumourgenesis, we plan to clarify how important deregulated Sprouty protein expressions are for the cellular transformation from normal to malignant cells.
Thereby we will analyse if and how modulated expression of Sprouty proteins influences deregulated cell proliferation, immortalisation and the cellular response to different signals.
Furthermore, we are interested in mechanisms involved in regulation of Sprouty expression during cell cycle, in response to different microenvironmental and in tumor development. This includes promoter studies as well as posttranscriptional regulation mechanisms like ubiquitination via c-CBL and other E3 ligases and mRNA regulation via microRNA-21.
Within this part of the project, we study the influence of miR-21 on Spry2 and Spry1 downregulation in cancer.
An additional aim of this project is to elucidate the role of miR-21 in cancerogenesis. This includes expression analysis as well as studies investigating the role of this small RNA in different cancers.