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Cells Re-Energize to Come Back From the Brink of Death

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 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. One of the requirements for apoptosis is activation of an enzyme called caspase.

The St. Jude team discovered that a cell that lacks caspase activation and cannot undergo apoptosis increases the levels of an enzyme called GAPDH in order to counteract the backup program called caspase-independent cell death (CICD). GAPDH appears to prevent CICD by supporting the functioning of the mitochondria and triggering the activity of certain genes that prevent or repair cell damage.

The findings also suggest that the increase in GAPDH provides energy to increase autophagy -- the process by which a cell 'chews up' debris and broken components, such as damaged mitochondria, said Douglas Green, Ph.D., chair of the St. Jude Immunology department and the study's senior author. After disposing of damaged mitochondria the cell can replace these vital components.


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