The renegade CK2 protein keeps the tumor alive and growing by desensitizing the cancer cells to the effects of another protein called TRAIL. Normally, TRAIL triggers apoptosis (cell suicide) in the cancer cells as a way of protecting the body. CK2 is an enzyme composed of four small proteins--two alpha proteins and two beta proteins.
The finding holds promise for developing drugs that help a patient's cancer cells become sensitized to TRAIL-induced apoptosis. For example, treating the tumors with TRAIL to trigger apoptosis while blocking CK2 might enhance anti-cancer treatment for a variety of other solid tumors, such as pediatric rhabdomyosarcoma, according to Janet Houghton, Ph.D., a member of St. Jude Hematology-Oncology. Rhabdomyosarcoma is a tumor originating in cells that have some features of muscle cells.
The St. Jude team showed that CK2 exerts its anti-apoptosis effect within a structure called DISC (death-inducing signaling complex). The DISC is a large jumble of proteins that interact with each other after TRAIL binds to the outer cell membrane. After DISC forms, an enzyme called caspase-8 triggers the cascade of biochemical events outside DISC that eventually leads to cell death. By desensitizing the cell to TRAIL, CK2 disrupts the DISC response, which in turn prevents apoptosis and allows the cancer cell to continue growing.
"The work my laboratory has done using our cell lines of colorectal cancer to investigate the role of CK2 in tumors is now bearing fruit," said Houghton, senior author of the Oncogene report. "We've shown in some detail how CK2 helps cancer cells survive the natural tendency for abnormal cell
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
23-Feb-2005