Written by Charlotte Harrison, Science Writer
A recent study in Nature Communications shows that not all cancer cells within a tumour metabolise glucose in the same way. The paper challenges the notion that cancer cells alter their metabolism to promote rapid growth, instead suggesting that altered metabolism can protect cells from damage.
Cancer cells use an unusual process to get energy. Unlike normal cells, which use mitochondrial metabolism, cancer cells rely on glycolysis (fermentation), even in the presence of sufficient oxygen and functional mitochondria. This phenomenon is often called the ‘Warburg effect’ after the biochemist who made the discovery back in 1924. Until now, it was largely accepted that glycolysis occurs so that cells can rapidly proliferate.
Despite much research to clarify how the metabolic adaptations of cancer cells contribute to tumour progression, surprisingly little is known about the role of metabolic reprogramming in cancer. To find out more, the researchers developed a fluorescent reporter that stained a marker of glycolysis and combined this with mass spectrometry imaging. Using mouse and organoid models of colon cancer, the authors found that not all cells within the colon cancer cell relied on Warburg glycolysis, only a heterogeneous group of quiescent cells.
“What really surprised us [was] the cells that were doing Warburg glycolysis were not dividing. This completely challenges the dogma of the Warburg effect,” said author Raul Mostoslavsky in a press release.
The authors showed that the rare population of cells undergoing Warburg metabolism had high pyruvate dehydrogenase kinase activity and expressed markers of intestinal stem cells and enteroendocrine cells. Further work showed that the non-dividing cells undergo active glycolysis to suppress the build-up of reactive oxygen species (ROS), which can otherwise damage cells. By enhancing glycolytic metabolism and reducing ROS, the cells increased their stem cell-likeness and tumorigenic potential.
Overall, the study shows that aerobic glycolysis protects non-dividing cells from damage. “[The Warburg effect occurs] not for the reason we used to think,” says Mostoslavsky. Moreover, the finding that aerobic glycolysis is a heterogeneous feature of cancer means that current technologies that analyse cell populations are of limited value. “[W]e need to rethink how we are studying cancer metabolism…. we now need to develop tools that will allow us to investigate tumours in a single-cell fashion”, he says.
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