Nature Cancer: The incidence of colorectal cancer is closely linked to gut microbes

A joint study by researchers from the VIB-UGent Center for Inflammation Research and the University of The ate reveals a new mechanism that causes colorectal cancerThe researchers found that abnormal expression of the Zeb2 protein affects the integrity of the intestinal wall or the epithelialTypically, this epithelial cell acts as a barrier against intestinal microbe stomonosThe Zeb2 protein destroys this barrier, allowing the permeable bacteria to cause inflammation, which can lead to the progression of cancerimportant, the researchers confirmed that controllingimmunesystem or removing the microbiome can inhibit the development of cancerThe findings could lead to new treatments published in the authoritative journal Nature Cancercolorectal cancercolorectal cancer is the third most common cancer and the fourth most deadly cancerUnfortunately, anticancer therapies, including immunotherapy, are relatively ineffective in colorectal cancerIn addition to genetic factors, environmental factors associated with Western lifestyles also increase the risk of colorectal cancerthe disease originated in the epithelial cells on the intestinal wall, and over time these "barrier" cells accumulate mutations and acquire malignant propertiesFor colorectal cancer, a deadly disease, a better understanding of the molecular mechanisms that lead to it is critical to the development of new treatmentsa new mechanism for the incidence of colorectal cancera team of researchers, Professor Geert van Loo, Lars Vereecke and Professor Geert Berx, found that zeb2 protein may be one of the causes of colorectal cancer They say that abnormal expression of Zeb2 in the epithelial cells of the intestines of mice can induce colorectal cancer The Zeb2 protein destroys the integrity of the intestinal barrier, allowing bacteria to penetrate tissue and trigger an immune response This leads to the abnormal proliferation of epithelial cells and eventually leads to the development of malignant bowel tumors Importantly, treating mice with broad-spectrum antibiotics , killing bacteria in the gut, or raising mice under completely sterile conditions, can completely prevent the development of cancer "We have studied the molecular mechanisms of tissue invasion and metastasis in a variety of cancers," says Professor Geert Berx We know that Zeb2 regulates a molecular process that allows cancer cells to acquire tissue aggression, leading to the progression of malignant diseases By using genetically modified mice expressing Zeb2, we can study this process in a number of tissues, including the intestines The study showed that Zeb2 recombined the epithelial cells of the intestinal wall, causing bacteria to pass through and cause inflammation, leading to tumors Professor Geert Berx, , added: "Recently, we established the first Belgian sterile mouse facility at ghent University to grow mice under completely sterile conditions Using this new technology, we can demonstrate that removing intestinal microbes from our models can prevent the development of colorectal cancer In addition, by regulating the activity of specific immune cells, we can also inhibit the development of cancer In summary, these findings demonstrate that complex immunological and microbial interactions have a significant impact on the development of colorectal cancer "
new therapy the new Zeb2 mouse colorectal cancer model is a unique tool for studying the interactions between tumors, immune and microorganisms and is useful for finding new treatments for colorectal cancer Since these mice's cancer development relied on microorganisms, sterile Zeb2 mice provided a unique preclinical platform for microbial research to identify cancer-promoting microorganisms, as well as to test new microbial-based treatments to prevent or treat colorectal cancer Professor Geert van Loo concluded: "We have identified the pathogenic mechanism with a new mouse model, but also confirmed the abnormal expression of Zeb2 in human colorectal tumor cells, which demonstrates the clinical significance of our model in human patients." From a scientific point of view, our findings are important because they help us understand why and how colorectal cancer occurs However, this recognition is also therapeutic and suggests that changing the microbiome or targeting specific immune components may be an effective strategy for developing new treatment sylloks for colorectal cancer "