Researchers at Vanderbilt Health have found that a balance of two closely related cell surface proteins may be critical to the health of the epithelial lining of the gastrointestinal tract, and for suppressing tumor formation in the colon.
The surface proteins are LRIG1, a tumor suppressor, and its cousin LRIG3, for which there have been conflicting reports about whether it cooperates with or opposes the action of LRIG1.
“We show that a balancing act between LRIG1 and LRIG3 keeps a powerful driver of colorectal cancer in check,” said Robert Coffey Jr., MD, Ingram Professor of Cancer Research and Professor of Medicine. “This offers potentially new avenues to explore in the treatment of colorectal cancer.”
Coffey is corresponding author of the report published Aug. 31 in the journal Cellular and Molecular Gastroenterology and Hepatology. Co-director of the Vanderbilt Epithelial Biology Center, he is internationally known for his research on mechanisms that drive the development of colorectal cancer, one of the nation’s leading cancer killers.
In 2012, Coffey and his colleagues found that removal of one copy of the Apc gene, the colon cancer “gatekeeper,” in LRIG1-expressing cells results in multiple colonic tumors.
Now they show that removal of both copies of theLrig3 gene in this setting drastically reduces tumor formation, highlighting the antagonistic nature of the LRIG proteins. This suggests that LRIG1 and LRIG3 work together to maintain the balance of cell signaling pathways implicated in cancer.
Matthew Bechard, PhD, was the paper’s first author. Other Vanderbilt co-authors were Zhengyi Chen, Ping Zhao, PhD, Radhika Aramandla, Yilin Yang, Alan Simmons, Kay Washington, MD. PhD, Jeffery Franklin, PhD, and Ken Lau, PhD.
The research was supported in part by the National Cancer Institute (grant R35CA197570), a GI SPORE grant (P50CA236733), and by the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.
