How Cancer Cells Rewire Their Metabolism to Survive

Jan. 31, 2013 — Researchers have discovered that tumors lacking the protein PKC? are good at surviving when nutrients are scarce -- opening a new therapeutic avenue that targets cancer metabolism.

Cells proliferating in an intestinal tumor

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 favorite food, a sugar called glucose. Unfortunately, this treatment approach not only fails to work, it backfires -- glucose-starved tumors actually get more aggressive. In a study published January 31 in the journal Cell , researchers discovered that a protein called PKC? is responsible for this paradox. The research suggests that glucose depletion therapies might work against tumors as long as the cancer cells are producing PKC?.

PKC?: critical regulator of tumor metabolism

According to this study, when PKC? is missing from cancer cells, tumors are able to use alternative nutrients. What's more, the lower the PKC? levels, the more aggressive the tumor.

"We found an interesting correlation in colon cancers -- if a patient's tumor doesn't produce PKC?, 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 tumor types," said Jorge Moscat, Ph.D., a professor at Sanford-Burnham. Moscat led the study in close collaboration with colleague Maria Diaz-Meco, Ph.D.

PKC? keeps tumors addicted to glucose, and under control

Although most cancer cells love glucose, tumors lacking PKC? grow even better in the absence of this nutrient. Using human tumor samples and a mouse model of colon cancer, Moscat and his team determined this growth-without-glucose paradox is because PKC?-deficient tumors are able to reprogram their metabolism to use glutamine, another nutrient, instead.

Without PKC? around to keep them addicted to glucose, these tumors kick-start a new metabolic pathway. This altered metabolism helps PKC?-deficient cancer cells survive in conditions that would otherwise be lethal.

"If we can find an effective way to add PKC? back to tumors that lack it, we'd make them less suited for survival and more sensitive to current therapies," Moscat said.