Researchers at Technical University Munich have reported findings related to the development of colon cancer. "We originally wanted to study the role of bacteria in the intestines in the development of intestinal inflammation," explains Professor Dirk Haller, Weihenstephan Science Centre.
"However, the surprising result for us was the discovery that bacteria, together with stress in cells, caused tumors (exclusively in the colon) and without the involvement of inflammation," said Haller.
The investigations were initially carried out using a mouse model. In germ-free animals in which the activated transcription factor ATF6 regulated stress in the intestinal mucosa (intestinal epithelium), no change could be observed.
But as soon as the microbiota were transplanted back into germ-free animals, tumors developed in the colons of the mice. Using Koch's postulates, Haller and his team were able to show that microorganisms are involved in the development of cancer in the colon.
The transcription factor ATF6 regulates stress in cells, and the intensity and duration of activation are increased with diseases. "However, it is not cell stress alone that leads to tumor growth, but the combination of stress and microbiota that favors cancer growth," says Haller, head of ZIEL—the Institute for Food & Health at TUM.
ATF6 incidence found to be increased in colon cancer patients
Subsequently, in cooperation with the clinic on the right side of the Isar (Prof. Janssen), the data of 541 patients with colon cancer were examined. In those cases in which the level of transcription factor ATF6 was significantly increased, triggering stress, the recurrence rate after surgery increased: About 10% of patients were at risk of developing colon cancer a second time.
"In certain patients, the protein ATF6 could serve as a diagnostic marker for an increased risk of colon cancer and could indicate the start of therapy at an early stage," said Prof. Haller—a microbial therapy is conceivable when we know more about the composition of the bacterial flora. What now became clear, however: Chronic inflammation has no effect on cancer development in the colon."
In patients with CRC, ATF6 was associated with the reduced time of disease-free survival. In studies of nATF6IEC mice, we found sustained intestinal activation of ATF6 in the colon to promote dysbiosis and microbiota-dependent tumorigenesis.