Scientists have uncovered a mechanism for protecting tumor cells from stress

Some tumor cells are able to survive the effects of chemotherapy due to a system of protection against oxidative stress. Scientists from Texas A&M University have found out how one of these mechanisms works and which enzymes control the activity of the URM1 protein. About how tumor cells protect themselves from damage and why this may affect the effectiveness of treatment, see the "Izvestia" article.

Why do tumor cells survive chemotherapy

Many anticancer drugs damage cells, including causing oxidative stress, a condition in which an excess of reactive oxygen species forms in the body. Such damage can be fatal for tumor cells, but some of them are able to activate their own defense mechanisms.

Researchers from Texas A&M University have studied one of the little-studied cellular pathways associated with the URM1 protein. The work was published in the journal Nature Communications. It was previously known that URM1 is involved in the response of cells to stress, but the mechanism of its activation in human cells has remained poorly understood.

Scientists have discovered that two enzymes, NAE1/UBA3 and UBE2M, are responsible for the modification of URM1. They trigger a process that allows URM1 to perform its function in the cell. The researchers also found that oxidative stress significantly enhances the activity of this pathway.

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How cells turn on protection from oxidative stress

To understand the work of URM1, the researchers developed a special molecular probe, with which they were able to detect the proteins involved in its activity. This is how scientists have established the role of NAE1/UBA3 and UBE2M.

When the activity of any of these enzymes was disrupted, URM1 function decreased dramatically. Scientists obtained a similar result when exposed to compounds that block the work of the corresponding enzymes. Additional experiments have shown that oxidative stress itself enhances URM1 modification. This means that the system is activated precisely in conditions when the cell needs to cope with damage.

The authors note that the discovered mechanism is related to previously known cellular processes. In particular, NAE1/UBA3 and UBE2M are involved in another type of posttranslational modification of proteins, niddylation. The new work shows that the same enzymatic cascade is involved in the modification of URM1.

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What happens when URM1 is blocked?

In the next step, the scientists tested how important URM1 is for cell survival under conditions of oxidative stress. To do this, they disrupted the activation of the corresponding pathway and compared the cells with a normally functioning defense system. It turned out that cells deprived of full URM1 activation were significantly worse able to tolerate oxidative stress. Their ability to survive the damaging effects decreased.

The result indicates the protective function of URM1: the protein helps cells adapt to conditions in which damage accumulates. This may be of particular importance for tumors, as some treatments use the ability of oxidative stress to damage cancer cells.

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How is the defense mechanism related to liver cancer?

The researchers separately examined the association of URM1 with liver cancer. To do this, they analyzed data on his activity and compared them with information about patients. It turned out that high URM1 expression was associated with lower survival in patients with liver cancer.

The authors suggest that this may reflect the ability of tumor cells to better adapt to oxidative stress and other damaging conditions. The liver is of particular interest for studying such a mechanism, since it is a metabolically active organ that is constantly exposed to processes associated with the formation of oxidative compounds.

However, the relationship found does not prove that high URM1 activity directly leads to a worse prognosis. The study shows a correlation and provides a basis for further study of the role of this protein in the development of tumors. The authors also emphasize that it is not yet known which proteins are the main targets of URM1 and how their modification affects the properties of tumor cells.

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Is it possible to use the vulnerability of the tumor in treatment

The discovery of a new mechanism may help scientists better understand why some tumor cells are able to survive damage that should lead to their death. If URM1 does provide protection against oxidative stress, disrupting this pathway could potentially increase the sensitivity of tumors to appropriate treatments.

At the same time, we are not talking about a ready-made method of therapy yet. The researchers have only identified the key enzymes involved in URM1 activation and shown the protective role of this mechanism in cellular experiments.

In addition, blocking such a pathway can affect not only tumor cells, but also healthy cells. URM1 itself has been preserved in various organisms for hundreds of millions of years, which indicates its important biological function.

According to Liu, identifying the enzymes that control the pathway provides researchers with the basis for further study of its role not only in cancer, but also in other diseases associated with cellular stress.