St. Jude Finds Link Between Cellular Defense Processes, Showing How Cancer Cells Survive

St. Jude Children's
Research Hospital investigators have discovered that immune system cells
that engulf and destroy germs in the body enlist help for this task from a
common housekeeping mechanism that most cells use to keep their interiors
healthy, a finding that is likely to help researchers understand how the
body defends itself against infections and how cancer cells can resist
chemotherapy drugs before they have a chance to work.


The discovery of this link between the two mechanisms --- phagocytosis
(engulfing germs) and autophagy (housekeeping) --- suggests that a common
mechanism that triggers both processes individually also links them
together using a common set of signals. The processes of phagocytosis and
autophagy enclose various cellular structures or germs within a sac that
fuses with a bag of digestive enzymes called the lysosome. The lysosome
then releases the digestive enzymes into the sac and the enzymes degrade
its contents. A report on the discovery appears in the Dec. 20 issue of the
journal "Nature."



The St. Jude team discovered that TLR, a protein on the surface of
cells that phagocytize germs, is the link between this "outside job" of
germ engulfment and the housekeeping "inside jobs" done by autophagy, such
as destroying germs that have forced their way into the cell and breaking
down defective molecules to obtain nutrients during times of stress.
Specifically, TLR recruits special proteins that orchestrate autophagy and
uses them to supervise phagocytosis and the formation of the digestive sac
called the phagosome.



"Our findings strongly suggest that TLR recruits parts of the autophagy
machinery to enable the phagosome to fully develop and fuse with the
lysosome even if autophagy itself doesn't occur simultaneously," said
Douglas Green, Ph.D., chair of the St. Jude Department of Immunology and
senior author of the report.



"Now that we discovered that phagocytosis uses some of the same
biochemical signals as autophagy does, we can use that information to solve
the mystery of how autophagy works," said Miguel Sanjuan, Ph.D., a staff
scientist in Green's laboratory and first author of the report.



Other authors of this paper include Christopher P. Dillon, Stephen W.
G. Tait, Simon Moshiach, Samuel Connell and Sebo Withoff (St. Jude);
Masaaki Komatsu and Keiji Tanaka (Tokyo Metropolitan Institute of Medical
Science, Japan); Frank Dorsey and John L. Cleveland (The Scripps Research
Institute, Jupiter, Florida).



This work was supported by the National Institutes of Health and ALSAC.



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

stjude