Scientists investigating a molecule known to play a key role in causing colon cancer have made a series of ground-breaking discoveries that could have major implications for future treatment of the disease, responsible for 655,000 deaths worldwide per year. Their findings are published in the journal Cancer Research, today (Wednesday 1 October 2008).
Led by Professor Janusz Jankowski the Sir James Black Professor of Gastrointestinal Biology and Trials at Barts and The London School of Medicine and Dentistry, researchers examined the cell adhesion molecule P-Cadherin. Having shown previously that this molecule is expressed in the mucous membrane of an inflamed intestine and colon, they wanted to better understand the mechanisms controlling its expression, and the biological effects of its unnatural presence in the intestine and colon. The P-Cadherin gene is important during early development, including in the formation of the foetus, but its actions are suppressed in the normal mature colon in adults. The repression of this gene in inflamed mucosa is lessened however, especially in stem cells, allowing the pockets of gut cells to form buds, enabling the damaged, inflamed mucosa to spread.
Now this latest research has revealed how the bowel becomes abnormal long before obvious changes are observable beneath the microscope, and how early pre cancer (10-15 years before it develops) expands within the bowel. The team have also highlighted the genetic and molecular mechanisms that switch on the gene, causing these processes to occur, and - in a model system - revealed how they are more likely to happen in an inflamed bowel than a non inflamed bowel. Their findings are a dramatic step forward in this field of cancer research and hold promise for future discoveries and therapies.
Colorectal cancer is the third most common form of cancer, and second only to lung cancer as the leading cause of cancer-related death in the Western world. Around 35,000 people a year are diagnosed with the disease in the UK, resulting in around 16,000 deaths.
Professor Jankowski said: "Understanding how a cancer develops so early in the disease gives great hope. If the changes in cell adhesion are understood and can then be identified so early in the disease then patients can be offered preventative therapy or even change of lifestyle to avert cancer developing at all."
- Milicic et al. Ectopic Expression of P-Cadherin Correlates with Promoter Hypomethylation Early in Colorectal Carcinogenesis and Enhanced Intestinal Crypt Fission In vivo. Cancer Research, 2008; 68 (19): 7760 DOI: 10.1158/0008-5472.CAN-08-0020
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