A Link Between Telomeres And Cancer Cells Found By New Study

A Link Between Telomeres And Cancer Cells Found By New Study

A new study published on the 11th of March reveals the way human cells recognize the damage suffered by their DNA. The study also reveals that cells can sense even only the possibility of future damage, which could lead to future dividing failure. Scientists have shown that telomeres, which are repetitive nucleotide sequences found at the end of each chromosome, protecting their ends from damage or fusion with neighboring chromosomes, transmit a signal announcing that the respective cell hasn’t divided in the proper time. The study was led by scientists from the Salk Institute for Biological Studies and was published in the journal Nature Structural and Molecular Biology.

The new information found by scientists has a major impact on chemotherapy. It shows how mitotic inhibitors (drugs used to slow the division of cancerous cells and ultimately destroy them) work and provides new ways to create drugs that could have a more potent effect on treating patients undergoing chemotherapy.

Telomere Caps

“How mitotic inhibitors work as cancer therapy has been a 25-year-old question. These drugs are widely used, but it was unclear why they actually kill cancer cells”, says professor Jan Karlseder, also the senior author of the study.

The laboratory that professor Karlseder runs has been studying the role of telomeres in cancer and the process of aging  for a long time. The first thing studied by the researcher team was the presence of specific proteins that would keep telomeres intact whilst going through the process of division. This was done by eliminating different proteins one by one whilst examining the telomeres by using fluorescent microscopy to determine whether or not they were damaged after the process was complete. Their findings were surprising: damaged, unprotected telomeres were observed in every cell that suffered the prolonging of cellular division through the elimination of specific proteins.

Scientist observed the same effect when using mitotic inhibitor drugs on the cells, thus leading them to formulate a new link between cellular death, slowed mitosis and telomere damage.

The study’s first author, Makoto Hayashi, says that telomeres are usually protected  by a protein called TRF2, which seems to disintegrate when the process of mitosis is slowed down due to different causes. He also says that with the help of his researcher team they have  discovered that during the slow down of mitosis, the protein, TRF2, disintegrates from telomeres, therefore exposing them and marking them as damaged DNA, which ultimately triggers the signal that informs about the damaged DNA.

Furthermore, the study revealed that extensive damage suffered by the telomeres leads to the activation of the p53 gene, which stimulates the tumor suppressor proteins. “DNA damage signals occurring during mitotic arrest likely predispose cells to upregulate p53 in the following phase. This then either halts the cell cycle to enable DNA repair to occur or commits cells to a suicide pathway called ‘apoptosis'”, says Makoto Hayashi.

Lead author, professor Karlseder adds that p53 is one of the most frequently found mutated pathways in cancer. Being the first to respond in the case of DNA or telomere damage, a dysfunctional p53 pathway could lead to the loss of genome integrity abnormal cellular mitosis and growth.

This new study suggests that a new approach in cancer chemotherapy should be investigated, an approach that would use the combined effect of two or more drugs in order to achieve better results than by using them alone. Scientists use the “triple cocktail” used to treat AIDS as reference to the powerful effect that the synergy between drugs can have in treating a patient.

Previous to professor Karlseder’s new study, telomeres were known to act as regulators for cell aging. Every time a cell divides, a small part of the telomere cap is also destroyed, eventually leading to the death of the cell. This is the process that ensures that a cell does not become cancerous or undying.

However, a few recent studies show that cancerous cells have the ability to surpass this protective measure and prolong their life by using different pathways that instead of reducing and ultimately destroying the telomere caps, they lengthen it, providing the cells with a longer life, thus leading to more divisions.