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Study could explain link between high-cholesterol diet and colon cancer



New research from the University of California Los Angeles (UCLA) could help explain the link between a high-cholesterol diet and an elevated risk for colon cancer. Scientists from the David Geffen School of Medicine have discovered that boosting cholesterol levels in mice spurred intestinal stem cells to divide more quickly, enabling tumors to form 100 times faster.

Their study identifies a molecular pathway that could serve as a new drug target for colon cancer treatment.

"We were excited to find that cholesterol influences the growth of stem cells in the intestines, which in turn accelerates the rate of tumor formation by more than 100-fold," said Peter Tontonoz, M.D., Ph.D., a UCLA professor of pathology and laboratory medicine. "While the connection between dietary cholesterol and colon cancer is well established, no one has previously explained the mechanism behind it."

The scientists increased cholesterol in the intestinal stem cells in some of the mice by introducing more of the substance into their diets. In others, they altered a gene that regulates phospholipids, the primary type of fat in cell membranes, which spurred the cells into producing more cholesterol on their own.

The stem cells' ability to multiply increased in both groups.

As the animals' cholesterol levels rose, their cells divided more rapidly, causing the tissue lining their guts to expand and their intestines to lengthen. These changes significantly sped up the rate of tumor formation in their colons.

The UCLA team will next explore whether the molecular pathway they discovered plays a similar role in accelerating the growth of other cancers. The current study is published online in Cell Stem Cell.


A pale-blue stain shows stem cells multiplying in a mouse's intestine. Image courtesy of Tontonoz lab/UCLA.

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DOI: 10.1016/j.stem.2017.12.017