(American Health Newswire) -- A new study provides insight into where colon cancer may come from and possible therapeutic targets for the disease.

A team of researchers are using a clinically engineered mouse model for colorectal cancer. Investigators can now use the mouse to better understand how and where colorectal cancer comes from. Colorectal cancer is the second leading cause of cancer deaths in the United States.

These tumors are thought to arise from a series of mutations in intestinal stem cells, which are long-lived, self-renewing cells that give rise to all cell types in the intestinal tract.

For more than 30 years, scientists believed that intestinal stem cells were mostly quiescent, proliferating only rarely in order to protect the tissue against cancer. However, in 2007, researchers reported finding a population of intestinal stem cells (marked by the molecule Lgr5) that were highly proliferative.

Those findings "really changed the way we think about intestinal stem cells," Robert Coffey, Jr., M.D., Ingram Professor of Cancer Research, co-chair of Vanderbilt's Epithelial Biology Center and senior author on the study, was quoted as saying.

"It came to so dominate the field that it raised the question about whether quiescent stem cells even exist...and that's where we enter into the picture."

Coffey and his team study the epidermal growth factor (EGF) signaling pathway - which includes a family of receptors known as ErbBs - and its role in cancers of epithelial tissues, like the intestinal tract.

Researcher Anne Powell, Ph.D., led the recent experiments showing that Lrig1, a molecule that regulates ErbB activity, is present in intestinal cells that have self-renewal and the ability to produce all the cells of the intestine).

"Essentially, what we show is that the Lrig1-expressing cells are stem cells and they are largely quiescent," Powell was quoted as saying.

"We also show that they're distinct from the Lgr5-expressing stem cells that had become a sort of 'hallmark' stem cell population...with different gene expression profiles and different proliferative status."

The team also showed that Lrig1 is not only a marker of intestinal stem cells, but also acts as a tumor suppressor and prevents the growth and proliferative signals of the ErbB family.

Fellow colleague Yang Wang, Ph.D., eliminated Lrig1 in mice and showed that nearly all of those mice developed intestinal tumors, providing further evidence suggesting that Lrig1 functions as a tumor suppressor.

The discovery downgrades the importance of ErbB signaling in the behavior of intestinal stem cells from which colorectal cancer may arise.

"Most exciting is that the mouse model his lab has generated as a part of these studies is one of the only mouse models to develop tumors in section of the intestines where most human tumors develop: the colon. One additional advantage of this model, in contrast to others, is that the tumors develop quickly and can be easily monitored with endoscopy, which will make it easier to assess how therapeutic interventions are working", Coffey was quoted as saying

SOURCE: Cell, March 29, 2012

(American Health Newswire) -- It is a known fact that sugar found in food is bad for teeth and the waistline, but now another sugar produced in the body's cells is implicated as a health hazard and blocking it may bring benefits that include treating cancer and improving long-term memory in older people.

The sugar is not table sugar, it is a substance produced in the body's cells that qualify as sugars because of its chemical standing. Its name is "oh-glick-nack," O-linked beta-N-acetyl glucosamine or "O-GlcNAc." It attaches itself to proteins that allow substances to pass in and out of the nucleus of cells and helps decide whether specific genes are turned on or off. In doing so, O-GlcNAc signals the basis of diabetes, cancer, Alzheimer's disease, and other disorders. Proteins with too much O-GlcNAc can not function normally.

Recent research on the sugar emerged from the use of advanced lab tools for probing a body process that involves attachment of sugars to proteins, called protein glycosylation. It coordinates the body and keeps it healthy by helping nerves and various cells communicate.

The study performed on mice developed a new process to screen the brain for all O-GlcNAc-glycosylated proteins. Over 200 proteins bearing the sugar attachments were identified. One O-GlcNAc effect on a particular protein was of significance to researchers.

CREB is a substance that turns on and regulates activity of the genes that are usually inactive in cells. Scientists found that when O-GlcNAc attached itself to CREB, CREB could not turn genes on. Researchers then blocked O-GlcNAc from binding to CREB and discovered that the mice would develop long-term memories faster as compared to normal mice.

"We're far from understanding what happens in humans. Completely blocking O-GlcNAc might not be desirable. Do you really want to sustain all memories long-term, even of events that are best forgotten? How would blocking the sugar from binding to other proteins affect other body processes? There are a lot of unanswered questions. Nevertheless, this research could eventually lead to ways to improve memory," Linda Hsieh-Wilson, Ph.D., with the California Institute of Technology was quoted as saying.

Also, in a related study, Dr. Hsieh-Wilson found that O-GlcNAc had interaction with another protein that would suggest the growth of cancer cells. By blocking its attachment, a smaller tumor was the result.

SOURCE: American Chemical Society, March 2012

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