The discovery of how some abnormal cells can avoid a biochemical program of self-destruction by increasing their energy level and repairing the damage, is giving investigators at St. Jude Children's Research Hospital insights into a key strategy cancer cells use to survive and thrive.
The finding offers an explanation of how abnormal cells that have cheated death once by disabling the main suicide pathway called apoptosis can also foil a backup self-destruct program, which allows them to survive and become cancerous.
The St. Jude study also suggests that a drug that disrupts a cancer cell's ability to block this backup program would allow that program to kill the cell. Such a specifically targeted drug might be more effective and less toxic than standard chemotherapy. A report on this work is in the June 1 issue of Cell."
Apoptosis is triggered by a variety of factors, including gene mutations that can make the cell become cancerous. During apoptosis, the membrane covering the cell's mitochondria develop holes and leak a molecule called cytochrome c, which triggers the activity of enzymes called caspases. In turn, caspases trigger a series of events that kills the cell. Mitochondria are tiny structures that act as power plants to supply the cell with energy, but also hold the keys to the cells, life and death.
The process by which the membranes develop holes,mitochondrial outer membrane permeability (MOMP) is often the ,point of no return, for self-destruction, said Douglas Green, Ph.D., chair of the St. Jude Immunology department and the study's senior author. MOMP triggers apoptosis, but if apoptosis fails because there is no caspase available, the backup program called caspase-independent cell death (CICD) takes over the process.
Previous research has shown that cells that become cancerous lack caspase and other proteins needed to support apoptosis after MOMP releases cytochrome c. But this victory over death is short-lived if CICD is activated. However, some cancerous cells not only dodge death from apoptosis by eliminating caspase activation, but they also foil CIDC. "Our study sought to understand how a cancer cell without caspase activation bypasses CICD as well," Green said.