The role of autophagy in regulation of cancer cell death

Macroautophagy (hereafter reffered to as autophagy) is a process of intracellular protein digestion in autophagolysosomes, allowing for removal of damaged proteins and preservation of energy and survival during metabolic stress, but also able to cause cell death when activated innapropriately. The main aim of the project is to establish the role of autophagy in therapy-induced death of cancer cells. The induction of autophagy and underlying molecular mechanisms will be investigated in cancer cell lines treated with various conventional (e.g. cisplatin, taxol, doxorubicin, imatinib) or experimental anticancer agents (e.g. metformin, statins, nanoparticles). The role of autophagy in therapy-induced tumor cell death will be analyzed using pharmacological inhibitors of autophagy or by blocking the expression of genes required for autophagosome formation. The relationship between autophagy and different types of cell death (apoptosis, necrosis), as well as molecular mechanisms responsible for autophagy-mediated regulation of cancer cell death (modulation of mitochondrial membrane potential, oxidative stress, signaling pathways and expression of genes that regulate cell cycle and death) will also be analyzed. Therapeutic potential of pharmacological modulation of autophagy will be investigated in vivo using experimental models of cancer or by analyzing autophagy induction in clinical tumor samples and its correlation with clinical and molecular prognostic markers.