Cancer cells need food to survive and grow. They're very good at getting it, too, even when nutrients are scarce.
Many scientists have tried killing cancer cells by taking away their favourite food, a sugar called glucose. Unfortunately, this treatment approach not only fails to work, it backfires—glucose-starved tumours actually get more aggressive.
In a study published in the journal Cell, researchers at Sanford-Burnham Medical Research Institute discovered that a protein called PKCζ is responsible for this paradox. The research suggests that glucose depletion therapies might work against tumours as long as the cancer cells are producing PKCζ.
PKCζ: critical regulator of tumour metabolism
According to this study, when PKCζ is missing from cancer cells, tumours are able to use alternative nutrients. What's more, the lower the PKCζ levels, the more aggressive the tumour.
"We found an interesting correlation in colon cancers—if a patient's tumour doesn't produce PKCζ, he has a poorer prognosis than a similar patient with the protein. We looked specifically at colon cancer in this study, but it's likely also true for other tumour types," said Jorge Moscat, Ph.D., a professor in Sanford-Burnham's National Cancer Institute-designated Cancer Center. Moscat led the study in close collaboration with Sanford-Burnham colleague Maria Diaz-Meco, Ph.D.
Although most cancer cells love glucose, tumours lacking PKCζ grow even better in the absence of this nutrient. Using human tumour samples and a mouse model of colon cancer, Moscat and his team determined this growth-without-glucose paradox is because PKCζ-deficient tumours are able to reprogramme their metabolism to use glutamine, another nutrient, instead.
Without PKCζ around to keep them addicted to glucose, these tumours kick-start a new metabolic pathway. This altered metabolism helps PKCζ-deficient cancer cells survive in conditions that would otherwise be lethal.
"If we can find an effective way to add PKCζ back to tumours that lack it, we'd make them less suited for survival and more sensitive to current therapies," Moscat said.
(EurekAlert, February 2013)
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