Cancer Cell Replacement Process Discovered

When cancerous cells die, they instruct neighboring cells to replace them.

For the first time, investigators have discovered how cells ensure they are replaced once they die, according to a study published by Developmental Cell. The discovery of the process could also lead to a novel approach against cancer.

“I believe this discovery is going to have important ramifications for cancer biology and cancer drug development, and for the treatment of other diseases, such as diabetic foot ulcers,” said study lead Sasha Shafikhani, PhD.

The team of researchers made the discovery when examining how a microbe kills cancer cells. The investigators previously explored how Pseudomonas aeruginosa can be lethal in patients who are wounded or sick.

They discovered that the bacterium secretes toxins that allow it to spur an infection, such as the ExoT toxin, which prevents cell division and slows wound healing, according to the study. While the toxin can be harmful, it has also shown promise against cancer cells.

When analyzing ExoT’s mechnisms against cancerous cells, the authors discovered how cells ensure that they are replaced.

Prior to cell death, surrounding cells are alerted that they need to be replaced to make sure the organism survives, according to the study. The authors report that this process has been explored with no conclusions for more than 2 decades.

The authors discovered what happened in the compensatory proliferation signaling (CPS) process. They found that dying cells release microvesicles that contain the Crkl protein. The microvesicle travels to neighboring cells and cause them to create new cells to replace the dying ones, according to the study.

Notably, the investigators found that knocking out the Crkl protein during CPS through genetics or with the ExoT toxin would stop the process. They reported that this is how P. aeruginosa exploits damaged tissues.

While cell death (apoptosis) is normal, the authors believe it could have significant importance for disease treatment.

“In the course of normal tissue turnover in humans, about one million cells die every second, through a highly-regulated process of apoptotic programmed cell death,” the authors wrote.

However, there are other types of cell death and not all cells undergo apoptosis.

These findings may be significant in the treatment of cancer. When cancer cells are dying due to treatment, they can call neighboring cells to replace it, making the treatment ineffective, according to the study.

The investigators hypothesize that if communication between dying cancer cells and neighboring cells is inhibited, cancer cells will not be replaced and the cancer would dissolve, according to the study.

For cancer, the CPS process would need to be inhibited, but the authors believe that the process could be amplified to increase wound healing. These findings may be used to develop new treatments for diabetic wounds, which are notoriously slow-healing.

“Knowing that it’s possible to uncouple CPS from apoptosis, we now can develop new drugs that would improve the effectiveness of treatments already in use,” Dr Shafikhani concluded.