Researchers at Åbo Akademi University have identified a new molecular change in patients with colorectal cancer and developed a genetic disease model that forms tumors in the large intestine, resembling those seen in patients. This novel model helps scientists better understand how the disease develops and supports the search for new treatments.
Colorectal cancer is becoming more common in younger people. To better understand the disease and develop effective treatments, researchers need models that closely resemble colorectal cancer in patients. Many existing models have limitations, for example, they include the use of carcinogens, developing tumors outside the large intestine, or they take a long time to develop.
Colonic epithelial cells form the protective barrier, separating the inside of the intestinal tube from the rest of the body. These cells divide at the highest rate of all cells in the body and completely renew the epithelial layer in 3-5 days. Colorectal cancer usually initiates when the colonic epithelial cells lose control over their normal rate of cell division partly due to changes in genes regulating cell division, such as the Adenomatous Polyposis Coli (Apc) gene.
Significant findings in previous studies from the research group have shown that a structural protein called keratin 8 protects the colonic epithelial cells from damage and inflammation. Keratin 8 is part of the cellular filament support system i.e. cytoskeleton and is essential for normal and healthy rate of cell division in the colon.
”Our new study identifies that keratin 8 levels are decreased in patients with colorectal cancer and the new model with low keratin 8 and Apc, resembles patients with colorectal cancer in several ways,” says doctoral researcher Mina Tayyab from the Biosciences and Drug Research program at Åbo Akademi University.
In the new disease model, researchers reduced the levels of keratin 8 and Apc selectively in cells lining the colon (colonic epithelium). Results show multiple tumors quickly forming in the lower (distal) part of the colon. This resembles colorectal cancer in patients, where tumors most often develop in the left or in the lower part of the colon. The tumors show key features and active signaling events that are typical of cancer development in epithelial cells. Decreasing keratin 8 levels alone lead to several tumor-promoting changes, including cells beginning to divide more and asymmetrically, losing their normal structure and orientation within the tissue.
In addition to the tumor-suppressive role of keratin 8 in the lower colon, the group identified that keratin 8 has a different role in the upper, or proximal part of colon, where keratin 8 protects from epithelial damage and inflammation.
”The new model, thus, not only reflects better the colonic epithelium in patients with colon cancer but also identifies different functions of keratin 8 in the proximal and distal colon. In addition, the model can be used for drug testing in colorectal cancer and provides a foundation for studying how keratin 8 protects different parts of the colon,” concludes Tayyab.
The Epithelial biology lab research group, led by Diana Toivola, Assistant Professor in cell biology at Åbo Akademi University, conducted the study in collaboration with Professor Yatrik M. Shah at the University of Michigan. The research was funded by the Academy of Finland, InFLAMES Flagship Programme, Åbo Akademi University Center of Excellence in Cellular Mechanostasis and Solutions for Health, National Institutes Health (NIH) as well as additional funding listed in the study.
The research article has been published in the scientific journal of Cellular and Molecular Gastroenterology and Hepatology on 24.12.2025. The article can be found here.