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Researchers identify link between colon cancer and metabolism
Date:5/13/2014

HEIDELBERG, 13 May 2014 More than 60 years ago Otto Warburg recognized that cancer cells differ from normal cells in the metabolic pathway they use for the oxidation of sugar. Rather than the typical series of oxidative steps that take place in the citric acid cycle, cancer cells metabolize sugar via the glycolytic pathway irrespective of whether oxygen is present or not. In The EMBO Journal, researchers in the United States report that the reason for this difference in colon cancer is changes in the Wnt signaling pathway, an essential communication pathway operating in these tumours.

"Cancer cells have different metabolic demands than normal cells," remarked Marian Waterman, Professor at the University of California, Irvine and the lead author of the study. "However, until now the molecular evidence for how this metabolic reprogramming takes place in cancers of the colon has not been very well defined. Our results show that Wnt signaling plays an important role in establishing aerobic glycolysis as the predominant sugar-metabolizing pathway to support colon cancer. We have also been able to identify one of the key molecular targets for the Wnt signal in cancer cells."

Wnt signaling has been implicated for some time in the development of many cancers, including colon cancer. However, these effects have been attributed to its action on the cell cycle. The researchers decided to investigate if Wnt had another role in cancer, specifically on metabolism, due to their observations of changes to the genes of metabolic enzymes in microarray experiments for colon cancer cells.

Biochemical assays and advanced imaging techniques in live cells revealed that blocking the activity of Wnt reduced glycolysis, promoted a shift to sugar metabolism by the citric acid cycle, and reduced tumour growth. The researchers also identified the enzyme pyruvate dehydrogenase kinase 1 as one of the targets for Wnt activity related to its effects on metab
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Contact: Barry Whyte
barry.whyte@embo.org
European Molecular Biology Organization
Source:Eurekalert

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