How cancer is protected from apoptosis
Scientists have found out why cancer cells don't kill themselves
The secret of the survival of many cancerous tumors is that they use the "fifth column" in their own DNA to suppress the work of the cell self-destruction system, according to an article published in the journal Nature Communications (Hu et al., A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay).
"Thanks to this discovery, we can now use the same algorithm to check whether the mechanism in the DNA of cancer tumors is broken in patients participating in the 100 thousand Genomes project. These observations can help us find new methods of fighting cancer that will save the lives of even more people in the future," says Christopher Yau from University of Birmingham (in the press release Cancer hijacks natural cell process to survive – VM).
A significant part of cancerous tumors in humans and animals occurs due to a breakdown in the p53 gene. It is responsible for protein synthesis, which monitors the integrity of genetic information and includes a self–destruction mechanism – apoptosis - in case of serious breakdowns. Cells with a damaged p53 gene are extremely difficult to suppress due to the lack of a "self-destruction program" in their genome.
Studies in recent years show that many cancer cells do not have fatal mutations in the p53 gene, but at the same time contain many other DNA breakdowns that usually cause it to turn on, Yau notes. It is also difficult to fight with such cells, since the usual methods of fighting cancer, including the destruction of DNA with radiation or chemotherapy, do not force them to "commit suicide".
British biologists have found out why this happens by studying the genomes of several hundred varieties of ovarian cancer. Initially, scientists tried to understand which mutations make cancer more aggressive, for this they compared sets of mutations for each tumor and identified those that most strongly influenced the behavior of cancer cells.
It turned out that about a fifth of the tumors – a very large number by the standards of cancer – mysteriously did not have mutations in the genes associated with the work of a special system that prevents the assembly of protein molecules when reading damaged genes.
This system, a set of several service proteins and ribosomes, cellular "protein factories", begins work after the nucleus counts the gene and prepares the so-called matrix RNA. It is a short template of the "letters" of the genetic code containing instructions for collecting a protein molecule.
Even before the mRNA leaves the nucleus, it is joined by special proteins-"inspectors" from the UPF family, who check whether it contains meaningless "typos" that lead to an unexpected interruption of protein synthesis. If there are such defects in the mRNA, then the proteins are firmly connected to the RNA molecule, which prevents the ribosomes from reading it, which leads to its subsequent destruction.
According to Yau and his colleagues, the correct operation of the "genetic spelling check" system in cancer cells does not kill them, but on the contrary, helps to survive. This is because UPF proteins block the reading of the p53 gene and prevent it from working even if it contains even relatively harmless mutations.
Having discovered such an unexpected mechanism of ovarian cancer survival, scientists have tried to find its analogues in cell cultures of other types of cancer. After analyzing over seven thousand other tumors, biologists have found hundreds of other examples of how this system helps cancer survive.
Therefore, Yau and his colleagues propose to create a drug that would block the "genetic spelling check" in cancer cells and allow p53 to launch a cellular suicide program. Such substances, according to scientists, could save the lives of many thousands of people whose cancer is now considered "invulnerable" to the action of classical methods of treatment.
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27.06.2017