Cancer-related targets sensed by apoptin

Lanz, H.L. (2012)

Doctoral Thesis

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 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.

• Mitotic catastrophe
• Proteasomal degradation
• Tumor-selective apoptosis
• Cancer
• Apoptin
• Proteins Killing Tumor Cells (PKTCs)

• All authors: Lanz, H.L.
• Supervisor: Noteborn, M.H.M.
• Co-supervisor: Backendorf, C.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2012-10-24