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.
De specifieke deletie van het SMAD4-gen in normale colonepitheelcellen van muizen die in vivo zijn gekweekt, verhoogde de expressie van ontstekingsmediatoren. Bij volwassen muizen met een ontsteking resulteert het ontbreken van SMAD4 in een verrassende overeenkomst tussen tumoren en kankers geassocieerd met colitis bij de mens.
Loss of SMAD4 was also observed in 48% of human colitis-related cancers, compared with 19% of scattered colorectale kankers. “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.
