Results from a new study suggest that a sensor protein called NLRC3 could play an important role in preventing the development of colon cancer.
The study, “NLRC3 Is An Inhibitory Sensor Of PI3K–mTOR Pathways In Cancer,” was published in the journal Nature.
NLRC3 belongs to the NLR family of sensor proteins, which regulate a wide range of biological functions, including certain features of immune cells. Previous studies have shown that colon cancer patients often have very low levels of NLRC3, suggesting that the protein plays a role in cancer development.
Researchers, led by Thirumala-Devi Kanneganti of St. Jude Children’s Research Hospital, used colon cancer mouse models to examine the role of the protein. The team found that, like in human patients, the animals had lower-than-usual levels of NLRC3, and that mice that lacked the gene encoding the protein were much more prone to develop colon cancer.
Results supported the idea that NLRC3 can protect colon cells from becoming cancer cells.
To understand how NLRC3 was exerting its protective effect, the researchers looked at the molecular pathways that were being regulated by the protein. They found that NLRC3 inhibited proteins from the PI3K-mTOR pathway, which controls cell proliferation, immune response, inflammation, and cancer. They also found that the pathway is activated early in the tumor-triggering process, suggesting that blocking its activation could prevent tumors from developing.
The PI3K-mTOR pathway plays a central role in cell signaling, so blocking it might not be feasible. Instead, the researchers believe that inducing the expression of NLRC3 could prevent PI3K-mTOR activation, and thus prevent tumor development in early stages.
“All of these complementary approaches to understanding NLRC3 allowed us to really nail it down that NLRC3 is important for protecting from abnormal colon cell growth, and when it is not present, tumors will develop,” Kanneganti, the study’s senior author, said in a news release. “This suggested that if we can somehow induce NLRC3 expression clinically, it will block the signaling pathways that lead to (tumor development).”