Nature Sub-Journal: Intestinal microbes through the broken intestinal wall cause colorectal cancer!

, June 26, 2020 /
BIOON/bio-valley-
-based research team from the VIB-UGent Inflammation Research Center at the Flanders Institute of Biotechnology in Belgium and a team at the University of Ghent has revealed a new mechanism for colorectal cancerThe researchers found that abnormal expression of the Zeb2 protein affects the integrity of the intestinal wall or the 'epithelial'"Normally, this epithelial cell acts as a barrier against intestinal microbes from penetrating." Zeb2 destroys this barrier and allows penetrationbacteriacause inflammation, which can lead to cancer progressionImportantly, scientists have shown that controlling the immune system or removing the microbiome can prevent the development of cancerThe findings could lead to new treatments and published in the journal Nature CancerPicture Source:Nature Cancercolorectal cancercolorectal cancer is the third most common cancer and the fourth deadliest cancerUnfortunately, anticancer therapies, including immunotherapy, have relatively low efficacy in colorectal cancerIn addition togeneticfactors, environmental factors associated with Western lifestyles, such as diet, obesity and sedentary lifestyles, also increase the risk of colorectal cancer the disease originated in the upper skin cells of the intestines Over time, these "barrier" cells accumulate mutations and acquire malignant properties A better understanding of the molecular mechanisms responsible for the development of colorectal cancer is essential to develop new treatments to effectively combat this deadly disease new mechanisms that cause colorectal cancer
a team of researchers, led by Professor Geert van Loo, Lars Vereecke and Professor Geert Berx, found that the Zeb2 protein may be one of the causes of colorectal cancer They found that abnormal expression of the protein in the intestinal epithelial cells of mice can induce colorectal cancer Zeb2 destroys the integrity of the intestinal barrier, allowing bacteria seep into tissue and trigger an inflammatory response This leads to the abnormal proliferation of epithelial cells, which eventually leads to the development of malignant intestinal tumor Importantly, treating mice with broad-spectrum antibiotics to kill the gut bacteria , or raising mice in completely sterile conditions, can completely prevent the development of cancer Professor Professor Geert Berx (CRIG/UGent) said: "We looked at the molecular mechanisms of attack and metastasis of different types of cancer tissue 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 and lead to inflammation, leading to tumor "There is growing evidence that microbes in our gutplay play a central role in human health and disease," said professor Lars Vereecke (VIB-UGent/CRIG) Many diseases are associated with significant changes in microbial composition, including colorectal cancer Functional studies are needed in mice to prove that the microbiome causes disease Recently, we established the first Belgian sterile mouse facility at ghret University to grow mice under completely sterile conditions Using this new technology, we can demonstrate that removing intestinal microbes in 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 Photo Source: New treatments Nature Cancer
new model of colorectal cancer the new Zeb2 mouse colorectal cancer model is a unique tool for studying the interaction of tumor -immune-microbes, 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 "We have identified the pathogenesis with a new mouse model, but also confirmed the abnormal expression of Zeb2 in human rectal tumor cells, which demonstrates the clinical significance of our model in human patients," concluded professor Geert van Loo ." From a scientific point of view, our findings are important because they help us understand why and how colorectal cancer develops However, this recognition is also therapeutic, suggesting that changing the microbiome or targeting specific immune components may be an effective strategy for developing new treatments for colon cancer " (biovalleybioon.com) reference: New mechanism underlying colorectal cancer reveals a nid role for the curmicrobes
Karolina Slowicka et al.
Zeb2 drives and microbiota-dependent colon carcinoma , Nature Cancer (2020) DOI: 10.1038/s43018-020-0070-2
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