Cell growth and division require the production of new proteins. This also applies to cancer cells. In a new study published in the journal Science Progress, researchers at the Carolinska Institute studied the protein eIF4A3 and its role in cancer cell growth. This study shows that by blocking or reducing the production of this protein, other processes can lead to the cessation of growth and cell division and ultimately death of cancer cells.
The normal cell division of the body is carefully controlled and genes in the cell are regulated as they begin and stop cell division.
Sometimes this balance is broken and cells continue to divide unchecked. After a while, a small percentage of cells begin to develop, and cancer may be about to form.
"When a cell grows, among other things, it produces new proteins by converting the cell's DNA information into mRNA, which forms the basis for protein production. The cell also needs to make ribonucleic acid for the cell's small factory, the ribosome. The ribosome is responsible for the production of protein," said Mikael Lindström, associate professor and collaborator in the research group of Professor Jiri Bartek in the Department of Medical Biochemistry and Biophysics at the Karolinska Institute, who conducted the research.
In this study, the team investigated cultured cancer cells and cancer tissues, in which the expression of eIF4A3 protein was higher than that of normal tissues.
By adding synthetic small molecules, which can later be further developed into finished drugs, the production of eIF4A3 can be examined. The researchers then found two different changes in cancer cells.
Dimitris Kanellis, lead author of the study and a postdoctoral fellow in the Department of Medical Biochemistry and Biophysics, said: "First, we found that blocking eIF4A3 activates the protein p53, a protein important in fighting cancer cells."
However, one challenge for many types of tumors is that the positive function of the p53 protein is counteracted by another protein, MDM2.
"Interestingly, we note that blocking eIF4A3 also implies a change in MDM2 protein. Dimitris Kanellis continued: "This change helps maintain and strengthen p53 and may be beneficial when we want to inhibit cancer cell growth." The main conclusion of the study suggests that deletion or inhibition of eIF4A3 activates p53 and alters the manufacturing process of proteins by disrupting ribosome biogenesis, thereby inhibiting the growth of cancer cells.
The understanding of the importance of eIF4A3 protein opens new opportunities for better and more effective treatment of cancer patients.
"The findings are very relevant because this targeted therapy may represent a new possible chemotherapeutic approach, for example in colon cancer, where cancer cells usually have high levels of ribosomes and rapid growth. Another example is sarcomas, cancers of the supporting tissues of the human body, which we know sometimes produce too much MDM2. This increases the chance of a more effective treatment," Mikel-LrdSr. Om and Professor Jiri Bartek said.
These studies provide an important basis for further research. However, since the study was mainly conducted in cultured cancer cells and clinical tumor material, it remains to be seen how blocking eIF4A3 will affect the growth of cancer in vivo.
“There may also be synergy between compounds that block eIF4A3 and drugs that we will now further investigate that have been used to treat cancer.”
