Inflammation causes colorectal cancer because of the loss of this protein

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Chronic inflammation is a  predisposing factor for colorectal cancer, which is the third leading cause of cancer-related deaths in the United States. Dr. Anna Means and colleagues reported in the journal Cell and Molecular Gastroenterology and Hepatology last month that they linked the inflammation-driven  carcinogenesis of the colon to the loss of an important signaling protein called SMAD4. SMAD4 is part of the transforming growth factor β (TGF-β) signaling pathway, which regulates the immune and inflammatory response to infection in the colonic epithelium.

The specific deletion of SMAD4 gene in normal mouse colon epithelial cells grown in vivo increased the expression of inflammatory  mediators. In adult mice with inflammation, the lack of SMAD4 results in a surprising similarity between tumors and cancers associated with human colitis.

Loss of SMAD4 was also observed in 48% of human colitis-related cancers, compared with 19% of scattered colorectal cancers. “This loss may be an important factor from premalignant lesions to aggressive malignant tumors,” the researchers concluded. Therefore, friends with chronic inflammation must eliminate inflammation in time, and do not regret it until the inflammation develops into cancer.


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