Cancer cells need a lot of nutrients to multiply and survive. While much is understood about how cancer cells use blood sugar to make energy, not much is known about how they get other nutrients.
Now, researchers at the Johns Hopkins University School of Medicine have discovered how the Myc cancer-promoting gene uses microRNAs to control the use of glutamine, a major energy source. The results, which shed light on a new angle of cancer that might help scientists figure out a way to stop the disease, appear Feb. 15 online at Nature .
"While we were looking for how Myc promotes cancer growth, it was unexpected to find that Myc can increase use of glutamine by cancer cells," says Chi V. Dang, M.D., Ph.D., the Johns Hopkins Family Professor of Oncology at Johns Hopkins. "This surprising discovery only came about after scientists from several disciplines came together across Hopkins to collaborate - it was a real team effort."
In their search to learn how Myc promotes cancer, the researchers teamed up with protein experts, and using human cancer cells with Myc turned on or off, they looked for proteins in the cell's powerhouse - the mitochondria - that appeared to respond to Myc. They found eight proteins that were distinctly turned up in response to Myc.
At the top of the list of mitochondrial proteins that respond to Myc was glutaminase, or GLS, which, according to Dang, is the first enzyme that processes glutamine and feeds chemical reactions that make cellular energy. So the team then asked if removing GLS could stop or slow cancer cell growth. Compared to cancer cells with GLS, those lacking GLS grew much slower, which led the team to conclude that yes, GLS does affect cell growth stimulated by Myc.
The researchers then wanted to figure out how Myc enhances GLS protein expression. Because Myc can control and turn on genes, the team guessed that Myc might directly turn on the GLS gene, but they found that wasn't the case. "So then we thought, maybe there's an intermediary, maybe Myc controls something that in turn controls GLS," says Ping Gao, Ph.D., a research associate in hematology at Johns Hopkins.