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Salk scientists open new window into how cancers override cellular growth controls
Date:3/21/2012

LA JOLLA, CA----Rapidly dividing cancer cells are skilled at patching up damage that would stop normal cells in their tracks, including wear and tear of telomeres, the protective caps at the end of each chromosome.

Loss of telomeres forces cells out of the dividing game and into a growth arrest state called "senescence," but cancer cells evade this by employing an enzyme called telomerase to extend eroded telomeres.

If telomerase fails to activate, the tumor cells of about 10 percent of all human cancers have a back-up strategy to build serviceable telomeres and keep dividing. How that pathway, called ALT for alternative lengthening of telomeres, works is unclear, because researchers have had limited options to study it experimentally.

Now scientists at the at Salk Institute for Biological Studies have created roundworms that eke out an existence, and even manage to reproduce, relying solely on ALT to maintain telomeres. That study, published March 16 in EMBO Journal, provides a valuable tool to tinker with the ALT pathway and learn how to block it, with a goal of forcing tumor cells to senesce.

"These worms are the first multicellular organisms we can study in the laboratory that maintain their telomeres through the ALT pathway and not through telomerase," says Jan Karlseder, a professor in Salk's Molecular and Cell Biology Laboratory and the study's senior author. "Up to now we could only study ALT in cell lines derived from tumor cells. Now we can screen for compounds and genes that suppress or regulate ALT in a whole organism, which in worms is fairly easy to do."

The components of telomere-building pathways are prime targets for cancer researchers. "There is a huge interest in drugs that block telomerase, since 90 percent of cancers use it for telomere maintenance," says Daniel Lackner, a postdoctoral fellow in the Karlseder lab and one of the study's first authors. "But these drugs won't work for the 10
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Contact: Andy Hoang
ahoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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