Researchers at Åbo Akademi University in Finland have developed a novel genetic model of colorectal cancer that replicates tumor development in the large intestine as seen in patients, offering a potentially significant tool for understanding the disease and testing new treatments. The findings, published December 24, 2025, in Cellular and Molecular Gastroenterology and Hepatology, address a critical need for more accurate models of colorectal cancer, a disease increasingly diagnosed in younger individuals.
Colorectal cancer originates in the epithelial cells lining the colon, which normally divide rapidly to maintain the intestinal barrier. Disruptions to this controlled cell division, often stemming from genetic mutations like those affecting the APC gene, are hallmarks of the disease. Existing models used to study colorectal cancer often rely on introducing carcinogens or fail to accurately mimic the disease’s progression and location within the intestine.
The Åbo Akademi team focused on the role of keratin 8, a structural protein previously identified by the group as protective against damage and inflammation in colonic epithelial cells. Keratin 8 is a key component of the cytoskeleton, which is essential for maintaining the structural integrity and regulated division of cells in the colon. Their new research demonstrates a correlation between decreased levels of keratin 8 and the development of colorectal cancer.
“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,” explained doctoral researcher Mina Tayyab. The researchers selectively reduced keratin 8 and Apc levels in cells lining the colon. This resulted in the rapid formation of multiple tumors, specifically in the distal, or lower, part of the colon – mirroring the typical location of tumor development in human patients.
The tumors generated in the model exhibited key characteristics and signaling pathways commonly observed in colorectal cancer. Reducing keratin 8 levels alone triggered tumor-promoting changes, including increased and asymmetrical cell division, and a loss of normal tissue structure. Interestingly, the research also revealed a distinct role for keratin 8 in the proximal, or upper, colon, where it primarily functions to protect against epithelial damage and inflammation.
“The new model, 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,” Tayyab stated. “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.”
The study was led by Diana Toivola, Assistant Professor in cell biology at Åbo Akademi University, and conducted in collaboration with Professor Yatrik M. Shah at the University of Michigan. Funding for the research was provided by the Academy of Finland, the InFLAMES Flagship Programme, the Åbo Akademi University Center of Excellence in Cellular Mechanostasis and Solutions for Health, and the National Institutes of Health (NIH). Further funding sources are detailed in the published study. Recent research has also highlighted the role of keratin 7 in inflammatory bowel diseases and its association with drug resistance [2, 4], suggesting a broader importance of keratin proteins in colorectal health.
