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Learning 1 of cancer's tricks
Date:8/23/2012

PASADENA, Calif. Behaving something like ravenous monsters, tumors need plentiful supplies of cellular building blocks such as amino acids and nucleotides in order to keep growing at a rapid pace and survive under harsh conditions. How such tumors meet these burgeoning demands has not been fully understood. Now chemists at the California Institute of Technology (Caltech) have shown for the first time that a specific sugar, known as GlcNAc ("glick-nack"), plays a key role in keeping the cancerous monsters "fed." The finding suggests new potential targets for therapeutic intervention.

The new results appear in this week's issue of the journal Science.

The research teamled by Linda Hsieh-Wilson, professor of chemistry at Caltechfound that tumor cells alter glycosylation, the addition of carbohydrates (in this case GlcNAc) to their proteins, in response to their surroundings. This ultimately helps the cancerous cells survive. When the scientists blocked the addition of GlcNAc to a particular protein in mice, tumor-cell growth was impaired.

The researchers used chemical tools and molecular modeling techniques developed in their laboratory to determine that GlcNAc inhibits a step in glycolysis (not to be confused with glycosylation), a metabolic pathway that involves 10 enzyme-driven steps. In normal cells, glycolysis is a central process that produces high-energy compounds that the cell needs to do work. But Hsieh-Wilson's team found that when GlcNAc attaches to the enzyme phosphofructokinase 1 (PFK1), it suppresses glycolysis at an early phase and reroutes the products of previous steps into a different pathwayone that yields the nucleotides a tumor needs to grow, as well as molecules that protect tumor cells. So GlcNAc causes tumor cells to make a tradethey produce fewer high-energy compounds in order to get the products they need to grow and survive.

"We have identified a novel molecular mechanism that cancer cells
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Contact: Brian Bell
bpbell@caltech.edu
626-395-5832
California Institute of Technology
Source:Eurekalert  

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