New Research Demonstrates How Cancer Cells Survive
US researchers have identified a novel metabolic pathway that helps cancer cells thrive in conditions that are lethal to normal cells.
The study found that cancer cells use an alternate version of two well-known metabolic pathways called the pentose phosphate pathway (PPP) and the Krebs cycle to defend against toxins. The toxins are reactive oxygen species (ROS) that kill cells via oxidative stress.
According to Dr Ralph DeBerardinis, the lead author of the study, normal cells and tumour cells grow by attaching to nutrient-rich tissue called a matrix. "They are dependent on matrix attachment to receive growth-promoting signals and to regulate their metabolism in a way that supports cell growth, proliferation, and survival.
His work found that Krebs cycle, a series of chemical reactions that cells use to generate energy, could reverse itself under certain conditions to nourish cancer cells.
"This study finds that two very different metabolic processes are linked in a way that is specifically required for cells to adapt to the stress associated with cancer progression." he said.
The research showed that cells use a "piggybacking" system to carry reducing equivalents from the PPP into the mitochondria. This movement involves an unusual reaction in the cytosol that transfers reducing equivalents from NADPH to a molecule called citrate, similar to a reversed reaction of the Krebs cycle, he said. The citrate then enters the mitochondria and stimulates another pathway that results in the release of reducing equivalents to produce NADPH right at the location of ROS creation, allowing the cancer cells to survive and grow without the benefit of matrix attachment.
However, Dr DeBerardinis said these findings were based on cultured cell models, and more research will be necessary to test the role of the pathway in living organisms.
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Reductive carboxylation supports redox homeostasis during anchorage-independent growth
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