Learning to manage entosis
MSU scientists are trying to turn cancer cells into "cannibals"
Scientists from MSU and the US National Cancer Institute have found out how one of the forms of cellular "cannibalism" works, which can be turned into a powerful weapon to fight cancer, according to an article published in the journal Scientific Reports (Garanina et al., Sequential entosis stages in human substrate-dependent cultured cells).
A significant part of cancerous tumors in humans and other 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 DNA damage. Therefore, cell cultures with a faulty p53 gene are extremely difficult to destroy due to the lack of a "self-destruction program" in their genome.
Apoptosis, as Galina Onishchenko from Lomonosov Moscow State University and her colleagues tell us, is not the only way of such self-destruction of cells that protects the body from the development of cancer. An alternative to it is the so–called entosis - a kind of cellular "cannibalism", in which one cell begins to eat its neighbors.
The initiator of this process is not the "cannibal", but the cell he eats – it independently penetrates into its neighbor and forces her to digest herself.
Entosis, as scientists believe today, is often one of the methods of "clearing the living space" that cancer cells use in the first phases of tumor development.
According to Russian biologists, it can also be used for the opposite purpose – the destruction of cancer, forcing its cells to eat each other. The realization of such a dream, as Onishchenko notes, is hindered by one simple thing – until now, scientists had no idea exactly how entosis works and how one cell learns that its neighbor "crawled" into it and that it needs to be "digested".
Researchers from Moscow State University and the USA managed to find the answer to this question by observing how skin and breast cancer cells multiplied in a test tube and periodically "ate" each other. As it turned out, entosis is a complex and multi-stage process consisting of five different phases, the successful completion of each of which is provided by a unique set of enzymes and signaling molecules.
For example, biologists have found that in order to successfully launch this process, it is necessary that a special set of protein tubes and filaments be present inside the eaten cell, and other parts of the cell play a key role in the work of other phases of entosis, during which the dying cell loses its shell, and its contents are gradually dissolved by the digestive enzymes of the "cannibal".
"We have demonstrated that entosis is possible not only when cells grow suspended in a liquid medium, but also when they attach to the substrate and to each other. For the first time, we discovered the stages of this process and the possibility of influencing certain stages," says Onishchenko.
The researchers hope that further study of this process will help us understand how to forcibly "turn on" a similar form of cellular self-destruction in cancerous tumors and force them to "eat themselves" in the literal sense, which will save the lives of people suffering from cancer, which is not affected by chemotherapy and apoptosis stimulants.
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