Some tumor cells may use a protein normally found only in the brain to help them survive and grow under stressful conditions, according to new findings. The protein, an enzyme known as carnitine palmitoyltransferase 1C (CPT1C), enables tumor cells to generate energy using fatty acids instead of glucose, which is the chief energy source for living organisms.
An international team of researchers led by Dr. Tak Mak of the University of Toronto published its findings May 15 in Genes & Development. The study suggests that CPT1C could be a new target for cancer therapy.
Cells within solid tumors, such as breast, lung, or colon cancers, can survive and grow under conditions that would kill normal cells. Tumor cells gain this survival advantage through alterations in their metabolism, a phenomenon known as metabolic transformation. Researchers have long known of this phenomenon but only recently uncovered evidence that fatty acids might be an energy source for tumor cells.
"It's like when the pipelines are cut for Middle East oil. You've got to tap all kinds of alternative sources for energy," explained Dr. James Phang of NCI's Center for Cancer Research, who studies cancer cell metabolism but was not involved in the current study.
The first hint that CPT1C could play a role in metabolic transformation came when Dr. Mak and his colleagues found that expression of the CPT1C gene was correlated with mouse mammary tumor cells' resistance to the anticancer drug rapamycin. The drug blocks glucose entry into cells and thus creates starvation conditions.
The researchers next asked whether CPT1C gene expression is increased in human cancers. They found that in 13 of 16 patients with non-small cell lung cancer, the levels of CPT1C messenger RNA (mRNA), which is used to make the CPT1C protein, were notably higher in tumor tissue than in normal lung tissue from the same patient.
In further experiments, the researchers showed that depriving tumor cells of nutrients or oxygen led to increased levels of CPT1C mRNA. They also showed that depleting CPT1C protein from human breast and colon cancer cells impaired the cells' ability to grow under low-oxygen and low-glucose conditions. CPT1C depletion also slowed the growth of tumors formed when the cancer cells were transplanted into mice.
Taken together, the study authors wrote, the results "suggest that a CPT1C inhibitor, used either…[alone] or in combination with other anticancer agents, may be a promising new avenue of cancer treatment."
In an interview, Dr. Mak said the larger implication is that rather than targeting oncogenes to treat cancer—a task that is daunting because of the sheer number of known oncogenes—it may be "time for us to try to exploit therapeutic targets, or combinations of therapeutic targets, that are a result of metabolic adaptation by a cancer cell...because there are fewer ways to rearrange the metabolic pathways of a cancer cell than there are oncogenes."
Dr. Phang agreed and noted that targeting CPT1C in particular "is promising as an approach to treating some cancers. But how efficient that could be and under what conditions remains to be seen," he said.
NCI Cancer Bulletin for May 31, 2011 - National Cancer Institute
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