Cancer is one of the most life-threatening diseases worldwide. Many anticancer treatments fail because they are not efficient or reveal too high side effects. Cancer cells develop due to unbalances... Show moreCancer is one of the most life-threatening diseases worldwide. Many anticancer treatments fail because they are not efficient or reveal too high side effects. Cancer cells develop due to unbalances in cell proliferation, cell cycle regulation and/or cell death. Identification of these aberrant molecular processes will reveal the essential processes leading to tumor formation and allows the generation of potential novel anticancer therapies. Interestingly, a group of viral and cellular proteins has been identified that harbors tumor-selective apoptosis activity. They are named Proteins Killing Tumor Cells (PKTCs). The aim of this thesis is to search for cellular processes sensed by the original PKTC, apoptin, which distinguish tumor cells from normal cells. Various tumor-related processes that are of importance for the tumor-selective activation of apoptin are reported. They range from proteasome activity and mitotic regulation to protein kinase and phosphatase action. The systematic analysis of both apoptin and other PKTCs reflects various differences between normal and tumor cells. Linking-up the various hallmarks of cancer with the aberrant processes sensed by apoptin and other PKTCs in cancer cells will hopefully contribute to a better understanding of tumor development as well as the generation of efficient and safe anticancer therapies. Show less
Cancer is one of the leading causes of death worldwide. Treatment is hampered by an incomplete understanding of the mechanisms underlying carcinogenesis and, consequently, by the absence of... Show moreCancer is one of the leading causes of death worldwide. Treatment is hampered by an incomplete understanding of the mechanisms underlying carcinogenesis and, consequently, by the absence of therapies to specifically eradicate cancer cells without harming normal, healthy cells. Intriguingly, the avian-virus derived protein apoptin was found to selectively induce apoptosis in transformed and tumor cells, heralding the advent of a new era in cancer treatment. The aim of this thesis was to discover the path followed by apoptin to distinguish between normal and cancer cells, and selectively kill the latter, in order to a) get to the root of the problem that is cancer, and b) provide the knowledge which is necessary to design novel, more selective, more effective, safe anti-tumor therapies. To this end, we identified a number of apoptin-interacting proteins, and studied their roles in tumor-selective apoptin-induced apoptosis. Show less
