The aim of these studies is to identify potential targets of experimental pharmacotherapy of cancer. The main focus is on signalling pathways generated by receptors (e.g. integrins, EGFR, IGFR), leading to activation of some enzymes (prolidase, proline oxidase), transcription factors (e.g. NF-kB, HIF-1α) and signalling proteins (e.g. FAK, AKT, mTOR, MAPK). MUB scientists study the role of proline metabolism in the regulation of apoptosis/autophagy in breast cancer, MCF-7 cells in order to identify target for pharmacologic regulation. Proline also plays an important role as an inhibitor of degradation of HIF-1α. The effect of this process is up-regulation of transcriptional activity of HIF-1α. One of the products activated by HIF-1α is vascular endothelial growth factor (VEGF) that activates angiogenesis. It is suggested that the induction of proline catabolism may be an important mechanism through which tumor cells switch to apoptosis or survival mode. The hypothesis may represent an approach to identifying molecular interface for experimental pharmacotherapy of cancer. Therefore their recent efforts are focused on studies on the role of proline metabolism in the mechanism of regulation of apoptosis and autophagy. The study approach involves analysis of deregulation of protein expression in cancer cells (receptors, signalling proteins, transcription factors) as well as metabolomic studies, particularly on proline and glutamine metabolites.
MUB Expert: professor Jerzy Pałka