Fatal Two-Way Combination Why colorectal cancer progresses and forms metastases

Disturbed collaboration between two genes causes colon cancer to progress

Colorectal cancer is one of the most common causes of cancer death in Germany, mainly due to metastases. Researchers have now found that the disrupted collaboration between two genes is partly responsible for this type of cancer progressing and forming secondary tumors.

One of the most common causes of cancer death

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

Researchers have found that in healthy people, two genes work together to prevent the development of colon cancer. However, if this cooperation is disrupted, the carcinoma progresses and forms metastases. (Image: Alex / fotolia.com)

Especially the metastases are dangerous

As tumors grow slowly in the large intestine or rectum and cause no problems for the majority of those affected for a long time, the disease is often recognized late.

Experts point repeatedly to the importance of the check-up, especially if it has come in the family already colon cancer cases. Early detection can save lives.

Because in the early stages can colon cancer, also called colon cancer, remove surgically.

Particularly dangerous are the metastases, which develop with the progression of the colon cancer.

As the Ludwig-Maximilians-Universität (LMU) Munich writes in a statement, they are the most frequent cause of death in patients.

Fatal combination investigated

As it goes on to say, changes in certain genes play a key role in the development and progression of colon cancer.

For every second colon cancer that causes metastases, both the Tp53 gene and the gene Mir34a are inactive.

Scientists led by Heiko Hermeking, Professor of Experimental and Molecular Pathology (also known as the German Consortium for Translational Cancer Research), have now investigated the consequences of this fatal combination in the mouse model and identified signaling pathways that could be therapeutic targets.

They report on their findings 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.

In healthy individuals, the two genes studied work together

In healthy people, the two genes studied work together to prevent just that. The two genes are said to suppress signaling pathways that promote the survival and invasiveness of cancer cells.

For example, miRNA microRNA miR-34a directly inhibits the IL-6 receptor IL-6R, which responds to the messenger interleukin 6 (IL-6) 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 in particular the protein Pai-1, which also contributes to the progression of the primary tumor.

The researchers demonstrated in mouse models 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.

Therefore, according to the study, these signaling pathways are interesting starting points for the treatment of colon cancer in humans, which should be followed in further studies from the researchers' point of view.

In addition, the study evaluated 628 cases of colorectal cancer in online databases and examined samples from 61 patients immunohistochemically.

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