Arginine – The Nutrient That Most cancers Cells Crave
Arginine is an amino
“It’s like if you had a LEGO set, and you’re trying to build a fancy model plane, and you run out of the right bricks,” says first author Dennis Hsu, a former member of Tavazoie’s lab and now a physician-scientist at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center in Pittsburgh. “The only way to still build the plane would be if you had altered blueprints that don’t require the missing bricks.”
The arginine-cancer connection
On a cellular level, arginine plays a role in a variety of processes, from nitrogen waste disposal to protein synthesis. It’s also one the few amino acids that has been shown to regulate how immune cells react to cancer and other sorts of immunologic triggers, Hsu says.
Its deficit, for instance, is linked to the inflamed tissues of people with Crohn’s disease, ulcerative colitis, inflammatory bowel disease, or an H. pylori infection, whose tissues can have low levels of arginine. If people with these conditions do not get treated, they have a higher risk of developing stomach or colon cancer.
The researchers uncovered the arginine-cancer connection as part of a larger study on codons, triplets of
In another experiment, Hsu found an increase in the number of mutations towards codons that produce amino acids that were more abundant in the environment of the cancer cells. These suddenly became more appetizing to the cancer cells, which seemed to be trying to make do with what they had—akin to cobbling together a meal out of a few random items that happen to be in your fridge.
Linking a specific nutrient to a specific DNA change through this sort of so-called directed evolution “had not been reported before to our knowledge,” Tavazoie says.
From red flag to bullseye
Interestingly, this ability to coax codons into doing their bidding could potentially lead to the cancer cells’ undoing. That’s because in the process of trying to keep themselves alive while malnourished, the cells accumulate so many mutations that they may begin to look very strange to the immune system.
“You have a bunch of random, abnormal-looking proteins because of all the mutations, and those are more likely to be recognized by the immune system as something that shouldn’t belong there,“ Hsu says. Once deeply mutated, arginine-starved cancer cells that might’ve been able to fly under the radar of the immune system might now be waving a tattered red flag at it.
The findings have potential implications for immunotherapy. “By starving a cancer cell, perhaps you can promote the gain of new mutations that can then be recognized by the immune system,” Hsu says. “We have not tested this, but it would be a really cool thing to try.”
Reference: “Arginine limitation drives a directed codon-dependent DNA sequence evolution response in colorectal cancer cells” by Dennis J. Hsu, Jenny Gao, Norihiro Yamaguchi, Alexandra Pinzaru, Qiushuang Wu, Nandan Mandayam, Maria Liberti, Søren Heissel, Hanan Alwaseem, Saeed Tavazoie and Sohail F. Tavazoie, 6 January 2023, Science Advances.