LAWRENCE A study recently published in the journal Carcinogenesis by researchers at the University of Kansas shows a new role for the protein adenomatous polyposis coli (APC) in suppressing colorectal cancer the second-leading cause of cancer-related deaths in the U.S.
Lead author Kristi Neufeld, associate professor in the Department of Molecular Biosciences and co-leader of the Cancer Biology program at the KU Cancer Center, has spent the better part of her career trying to understand the various activities of APC, a protein whose functional loss is thought to initiate roughly 80 percent of all colon polyps, a precursor to colon cancer. Neufeld, along with her postdoctoral fellow Maged Zeineldin, undergraduate student Mathew Miller and veterinary pathologist Ruth Sullivan, now reports that APC found in a particular subcellular compartment, the nucleus, protects from inflammation as well as tumor development associated with chronic colitis.
Whether APC reaches the nucleus may well affect the ability of intestinal stem cells to produce differentiated cells with specialized functions, Neufeld said.
"It's not widely appreciated, but there is still plenty of cell growth going on in adults, with the colon being a good example," she said. "On average, we shed and replace about 70 pounds of intestinal tissue annually, so you can imagine that this process requires exquisite control to prevent tumor formation."
Regular renewal of the colon lining occurs through stem cells that are capable of constantly dividing. These cells produce descendants that take up specific roles: By secreting mucin, for instance, goblet cells generate a mucus layer that serves as the colon's physical barrier against its many microbial tenants. But if APC can't find its way to the nucleus, Neufeld and her team have noted far fewer goblet cells as one outcome.
"We introduced a specific APC mutation into mice that took away the nuclear
|Contact: Brendan M. Lynch|
University of Kansas