Glycine and cancer proliferation
May 24, 2012 § Leave a comment
It may be the smallest of the 20 amino acids, but glycine appears to push the multiplication of cancer cells. In a paper just out in Science, Vamsi Mootha at Harvard Medical School and colleagues found that glycine consumption and expression in the mitochondrial glycine biosynthetic pathway closely matched the rates of cancer cell proliferation.
The investigators used mass spectrometry to track the consumption and release profiles of 219 metabolites in 60 cancer cell lines. They integrated their metabolite data with an atlas of gene expression that already had been put together. “Once we generated the profiles, we simply chased the data, without any preconceived hypotheses,” says Mootha. Their analysis revealed that, out of the 219 metabolites, glycine was the key one.
When Mootha and colleagues took steps to prevent glycine uptake or to stop the mitochondria from making it, they discovered that they slowed down the multiplication of cells. Mootha says he and his colleagues were startled to find that across the 60 cell lines they studied the consumption and release of glycine and its biosynthesis in mitochondria were correlated to rates of proliferation. Glycine long has been known to be a key precursor to many of the cell’s building blocks, “but that there ought to be such a strong correlation, and that disrupting it slows down rapidly proliferating cells, was a surprise,” he says.
Uwe Sauer at the Swiss Federal Institute of Technology Zurich, who wasn’t part of Mootha’s team, agrees the finding is unexpected. “We simply had no idea that glycine metabolism was so intricately and robustly related to rapid proliferation in normal and cancer cells,” he says.
Mootha and colleagues speculate that targeting the glycine biosynthetic pathway in cancer cells may provide a way to attack the disease’s progression.
But Mootha reminds us that the work is just the beginning. The next stages of research require figuring out how the various pathways in which glycine is involved are compartmentalized in cells. “Understanding the compartmentalization is an important basic science question,” says Mootha.
He also points out that researchers need to spend more time working out how the different pathways that use glycine play into tumorigenesis.