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.



Other authors of this study include Anna Colell (Institut
d'Investigacions Biomediques de Barcelona, Spain); Jean-Ehrland Ricci
(Universite de Nice Sophia, Antipolis, France); Stephen Tait, Sandra
Milasta, Lisa Bouchier-Hayes, Patrick Fitzgerald and Helen M. Beere (St.
Jude); Ana Guio-Carrion, Cindy Wei Li and Donald D. Newmeyer (La Jolla
Institute for Allergy and Immunology, San Diego); Nigel J. Waterhouse
(Peter MacCallum Cancer Centre, Melbourne, Australia); and Bernard Mari and
Pascal Barbry (Institute de Pharmacologie Moleculaire et Cellulaire, Sophia
Antipolis, France).



This work was supported in part by the National Institutes of Health
(DRG); Association pour la Recherche Contre le Cancer; Fondation pour la
Recherche Medicale grants (JER); and Plan Nacional I+D+I grant (AC). AC
received a fellowship from the Secretaria de Estado de Universidades e
Investigacion of Spain.



St. Jude Children's Research Hospital



St. Jude Children's Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and
other catastrophic diseases. Founded by late entertainer Danny Thomas and
based in Memphis, Tenn., St. Jude freely shares its discoveries with
scientific and medical communities around the world. No family ever pays
for treatments not covered by insurance, and families without insurance are
never asked to pay. St. Jude is financially supported by ALSAC, its
fundraising organization. For more information, please visit
stjude.


St. Jude Children's Research Hospital

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