Aristidis Moustakas research group

TGF-β SIGNALING AND CANCER CELL DIFFERENTIATION

An important goal in cancer research is the study of mechanisms that control the signaling pathways of growth factors. Such mechanisms include enzymes, i.e. proteins that help the catalysis of chemical reactions in our cells. This research has a major impact because the pharmaceutical industry uses this mechanistic information in order to generate new drugs that control the activity of these enzymes. Intense research has generated basic knowledge on the biology of cancer. However, such knowledge is significantly less with respect to the capacity of tumor cells to metastasize. Research in this area will lead to the development of new anti-cancer therapies, where blocking metastasis is the central focus.

We study the ability of tumor cells to transform from differentiated epithelial cells to metastatic cells and the relationship of such transformations to the gain of stem cell features. Transforming frowth factor beta and bone morphogenetic protein are important growth factors that regulate the transformations of cancer cells. We also study analogous processes in brain tumors, like glioblastoma and meduloblastoma.

Our research focuses on the family of growth factors that are known as transforming growth factor beta (TGFbeta), which include proteins like TGFbeta and bone morphogenetic proteins (BMP). TGFbeta or BMP regulate many different biological processes in the human body, e.g. cell division, differentiation and cell death. TGFbeta is secreted from cells and binds to receptors on the cell surface. The receptors activate Smad proteins inside the cells. The signaling pathway of TGFbeta is regulated by many different proteins that ensure that the molecular signals perform their function properly. Such regulatory mechanisms are the most frequent defects developed by cancer cells.

In vitro cell models together with modern high-throughput technology facilitate our research to bridge to the clinical applications. The most central cell biological aspects of our research programs include gene regulation and epigenetic mechanisms, non-coding RNA, cell polarity protein complexes, secretion of extracellular vesicles and 3D tumor organoids. We anticipate to identify new basic mechanisms that regulate the differentiation of cancer cells and their invasive potential as well as mechanisms that support the generation of stem cells. We also aim at studying how different chemicals can inhibit tumor cell migration and invasion. Such chemicals can be the seed for future development of drugs against cancer metastasis.

In summary, our research programs leads to a deeper understanding of how molecular mechanisms regulate important biological processes, such as signal transduction and cell differentiation.