Cancer and Glycolysis

Cancer and Glycolysis - Frontiers in Cancer Research NEWS...

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26 MAY 2006 VOL 312 SCIENCE www.sciencemag.org 1158 CREDIT: RICHARD K. J. BROWN/UNIVERSITY OF MICHIGAN HEALTH SYSTEM I n a widely cited paper published 6 years ago, cancer biologists Robert Weinberg of the Massachusetts Institute of Technology and Douglas Hanahan of the University of California, San Francisco, described six hallmarks of cancer cells, including their ability to invade other tissues and their limitless potential to replicate. Last month, at the annual meeting of the American Association of Cancer Research, Eyal Gottlieb launched a lecture with this provocative claim: “I believe I’m working on the seventh element, which is bioenergetics.” Gottlieb, a biologist at the Beatson Institute for Cancer Research in Glasgow, U.K., notes that tumor cells need an unusual amount of energy to survive and grow. “The overall metabolic demand on these cells is significantly higher than [on] most other tissues,” he says. Tumors often cope by ramping up an alterna- tive energy production strategy. For most of their energy needs, normal cells rely on a process called respiration, which consumes oxygen and glucose to make energy-storing molecules of adenosine triphosphate (ATP). But cancer cells typically depend more on glycolysis, the anaerobic breakdown of glucose into ATP. This increased glycolysis, even in the presence of available oxygen, is known as the Warburg effect, after German biochemist Otto Warburg, who first described the phenomenon 80 years ago. Warburg thought this “aerobic glycolysis” was a universal property of cancer, and even its main cause. Warburg won a Nobel Prize in 1931 for his earlier work on respiration, but his cancer theory was gradually discredited, beginning with the discovery of tumors that didn’t display any shift to glycolysis. Ultimately, the ascendancy of molecular biology over the last quarter- century completely eclipsed the study of tumor bioenergetics, including Warburg’s ideas. The modern view of cancer is that it’s a disease of genes, not one of deranged energy processing. Now, a revival in research on tumor bio- energetics suggests it could be both. A growing stream of papers is making the link between cancer genes and the Warburg effect, indicating that bioenergetics may lie at the heart of malignant transformation. For example, in a paper published online by Science this week (www.sciencemag.org/cgi/content/abstract/ 1126863), Paul Hwang’s group at the National Heart, Lung, and Blood Institute in Bethesda, Maryland, reveals that p53 , one of the mostly commonly mutated genes in cancer, can trigger the Warburg effect. And last year, Arvind Ramanathan and Stuart Schreiber of the Broad Institute in Cambridge, Massachusetts, reported that in cells genetically engineered to become cancerous, glycolytic conversion started early and expanded as the cells became more malignant. They concluded that the cancer- gene model and the Warburg hypothesis “are intimately linked and fully consonant.” This idea remains controversial. Weinberg,
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This note was uploaded on 09/06/2009 for the course BIS 103 taught by Professor Abel during the Spring '08 term at UC Davis.

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Cancer and Glycolysis - Frontiers in Cancer Research NEWS...

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