A normal cell shields itself against the buildup of a faulty chromosome by never reproducing anymore once it has been damaged by DNA.
During inflammatory circumstances, though, those preventive processes are disrupted, which increases the formation of intestinal cancer. It’s still unclear why some defensive mechanisms break down in the face of persistent inflammation.
How Cancer Is Caused By Prolonged Intestinal Inflammation
Different types of cancers prove fatal for the human lives who have to suffer from them. In a study led by some of the experts in this field, it is checked that intestinal inflammation for a longer term may lead to cancer.
The group of specialists has checked a number of samples with different levels of health and found almost the same results in each sample that has led to believe this fact.
Chronic inflammatory bowel disease (IBD) is characterized by intestinal inflammatory that flares up in stages and is followed by bloody stools, diarrhea, as well as a substantial reduction in the standard of life. Individuals with IBD are more likely to acquire colon malignancy. This is aided by the reality that prolonged inflammation activities harm DNA in gastrointestinal mucosal cells.
“If the IBD risk gene XBP1 is missing in intestinal epithelial cells, then DNA damage and increased cell division will occur. Animals with a defective XBP1 gene developed invasive intestinal cancer,” reported the first author Lina Welz.
A group at PMI’s Cluster of Excellence, “Precision Medicine in Chronic Inflammation” (PMI), have discovered that IBD susceptibility factor XBP1 has a significant impact on the way a gastrointestinal mucosal cell responds to DNA damages & so shields itself off tumor growth. The tumor protector p53 and the mTOR signaling system are involved in the process.
The scientists sought to know exactly what method the genes XBP1 utilizes to control DNA repairs that, as a result, contribute to cancers in the case of XBP1 dysfunction. The scientists revealed that the well-known genetic switch p53, also called a tumor suppressor, plays a vital function in protecting cells against cancerous deterioration.
“Our results indicate that XBP1 and p53 work together via the so-called mTOR signaling pathway to prevent a damaged intestinal epithelial cell undergoing uncontrolled proliferation, and thus becoming malignant,” said one of the senior authors PD Dr. Konrad Aden.
A possible treatment strategy
“Although we have known for a long time that cancer can arise from chronic intestinal inflammation, we only know relatively little about the underlying processes. Our results now provide a new link between inflammation, disturbed cell division, and repair of genetic material,” reported senior author Professor Philip Rosenstiel, director of the IKMB.
“We will, therefore, in further studies investigate how targeted inhibition of the mTOR signaling pathway can be used to prevent intestinal inflammation and cancer,” said Rosenstiel.
The mTOR signaling system had already been exploited as a therapy focus for various illnesses in healthcare, and it may now give a fresh window of opportunity for tumor therapy. The scientists used Rapamycin, a pharmaceutical drug that inhibits the mTOR system, to cure mice with cell systems having elevated DNA damages and faulty XBP1 genes. “In our models, Rapamycin significantly reduced the increased cell division and the resulting damage to the intestinal epithelium,” reported Aden.
“This scientific success of a clinician-scientist at the cluster also proves the effectiveness of the clinician-scientist program in the Cluster of Excellence PMI, which enables physicians to research an equal basis at the same time as their specialist medical training.
The freedom to research created in this way and the good scientific infrastructure enables clinically active doctors, such as Lina Welz, to achieve such outstanding scientific achievements,” emphasized Professor Stefan Schreiber.
