New research, published in the «eLife», showed that the multiplication of cancer cells in the absence of appropriate growth stimuli supported additional loss of p53 protein in the tumor. This guarantees that the replication of the genetic material, DNA continues. This discovery will help to understand how cancer cells survive and thrive in adverse conditions, and identify potential methods of blocking these mechanisms.
When a cell divides, its DNA is replicated and the two copies are distributed between the two daughter cells. Any problems that occur during the replication process can cause damage to DNA, which in turn can cause growth arrest and cell death. Therefore, a healthy cell DNA can play only under favorable conditions - when there are certain growth stimuli.
"In the absence of growth factors, such as inadequate blood supply, a normal cell includes" secure lock "that blocks cell in the G1 phase of the first division cycle. This ensures that the DNA is not replicated. Most cancer cells do not have this "Safety Locking", also referred to as checkpoints G1, so they can begin to replicate DNA without growth stimulus. But cancer cells pay a high price for such a replication - their DNA is damaged due to replication problems, and it includes a second "safety lock", which can lead to growth arrest and cell death. It is not yet entirely clear how tumor cells overcome all these obstacles and support the growth of cancer "- the researchers noted.
In addition to the loss of checkpoint G1, some of the most common mutations occur in p53 protein plays a central role in the second protective retainer. It is believed that p53 loss helps cancerous cells survive.
New research has shown that the lack of growth stimulus, with the lack G1 checkpoint cells actually "suffer" from the problems caused by the replication of DNA. They also found that the simultaneous lack of p53 reduces the damage caused by the replication problems during DNA replication, allowing cancer cells to proliferate in adverse conditions. These findings may explain the partial loss of p53 in cancer cells, which lack the checkpoint G1.
Although p53 loss reduces DNA damage, the cell is still experiencing serious problems with replication. "Most likely, cells rely on mechanisms that support the replication of DNA to a level sufficient to complete the process without undue damage, thereby creating a" Achilles' heel "of cancer cells. In the future, we plan to study these mechanisms and to find out whether pharmacological intervention in this process to assist in the treatment of cancer "- the researchers reported.