Fatal combination of two: why colorectal cancer progresses and forms metastases

Fatal combination of two: why colorectal cancer progresses and forms metastases

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Disordered collaboration between two genes allows colon cancer to advance

Colon cancer is one of the most common causes of cancer death in Germany due to its metastases. Researchers have now found that the impaired collaboration of two genes is partly responsible for the fact that this type of cancer progresses and daughter tumors form.

One of the most common causes of cancer death

According to health experts, colorectal cancer is the third most common cause of cancer death for men after prostate and lung cancer and the second most common cause of cancer death for women after breast cancer in Germany. Around 26,000 people die of it every year in Germany. The chances of recovery depend heavily on how early the cancer is discovered. And also whether he has already spread. But why does colon cancer often progress rapidly and why does the carcinoma form metastases? This also has to do with the disturbed collaboration of two genes, as researchers have now found out.

The metastases in particular are dangerous

Since tumors in the large intestine or rectum grow slowly and do not cause any problems for a long time for most of those affected, the disease is often recognized late.

Experts therefore repeatedly refer to the importance of the preventive medical check-up, especially if the family has already suffered from colon cancer. Early detection can save lives.

Colon cancer, also known as colon carcinoma, can be surgically removed at an early stage.

The metastases that develop as the colon cancer progresses are particularly dangerous.

As the Ludwig Maximilians University (LMU) Munich writes in a statement, they are the most common cause of death among patients.

Fatal combination examined

As they say there, changes in certain genes play an important role in the development and progression of colon cancer.

In every second colon cancer, as a result of which metastases develop, both the Tp53 gene and the Mir34a gene are inactive.

Scientists around Heiko Hermeking, Professor of Experimental and Molecular Pathology (also German Consortium for Translational Cancer Research), have now examined the consequences of this fatal combination in the mouse model and identified signaling pathways that could be therapeutic starting points.

They report on their results in the journal "Gastroenterology".

"The loss of both genes increases the frequency and development of intestinal tumors, as well as their invasion into the surrounding tissue and the subsequent formation of metastases in colon cancer," explains Heiko Hermeking.

The two genes examined work together in healthy individuals

In healthy people, the two genes examined work together to prevent exactly this. According to the information, the two genes suppress signaling pathways that promote the survival and invasiveness of cancer cells.

For example, the miR-34a microRNA directly inhibits the IL-6 receptor IL-6R, which reacts to the messenger interleukin 6 (IL-6), which is produced by the tumor environment, and triggers the so-called epithelial-mesenchymal transition (EMT) .

EMT is an essential mediator of metastasis. In addition, the simultaneous loss of p53 and miR-34a activates the protein Pai-1, which also contributes to the progression of the primary tumor.

In mouse models, the researchers were able to show that therapeutic inactivation of the IL-6R and the PAI-1 signaling pathway prevents the formation of metastases in p53 and miR-34a-negative intestinal tumors.

According to the study, these signaling pathways are therefore interesting starting points for therapy for colon cancer in humans, which the researchers believe should be pursued in further studies.

In addition, 628 cases of colon cancer were evaluated in online databases and samples from 61 patients were examined immunohistochemically.

According to the analysis, the results from the preclinical mouse model are transferable to humans. (ad)

Author and source information

Video: Lindseys story: Colon cancer warning signs (October 2022).