Nature: The Nobel Prize winner recently discovered that organisms can actually squeeze to remove cancer cells, bringing new ideas for cancer treatment

For all animals, removal of certain cells is necessary for embryonic development, and living cells will naturally fall off in mature tissues.

One way for organisms to remove unwanted cells is through a process called cell extrusion, which squeezes cells out of the tissue layer without destroying the remaining cell layer.

On May 5, 2021, the Nobel Prize winner and MIT Professor Robert Horvitz team published a research paper titled: Replication stress promotes cell elimination by extrusion in the Nature journal.

Researchers in C.

Cell squeezing is a cell removal mechanism used by organisms from sponges to insects to humans.

Apoptosis

In the 1880s, Professor Robert Horvitz began to study a type of programmed cell death called apoptosis, in which organisms use apoptosis to eliminate cells they no longer need.

Professor Robert Horvitz used the C.

In 2002, Robert Horvitz, Sydney Brenner, and John Sulston won the Nobel Prize in Physiology or Medicine for discovering the genetic regulation mechanism of organ development and programmed cell death.

Later, Professor Robert Horvitz's team discovered that if nematodes cannot clear cells through apoptosis after genetic mutation, then a small number of these 131 cells will be cleared by cell extrusion, which seems to be a backup for apoptosis mechanism.

However, how to trigger this cell extrusion process is still a mystery.

Get into the cell cycle

In order to solve this mystery, the research team conducted a large-scale genetic screening, screening a total of more than 11,000 Caenorhabditis elegans genes.

Surprisingly, many genes that are essential in the cell extrusion process are involved in the cell division cycle at the same time.

Further experiments showed that the cells that were eventually squeezed out did start to enter the cell cycle and began to copy their DNA.

Most of the cells that are eventually squeezed out are abnormally small.

The red cell in the middle is being squeezed out of the embryonic tissue of the nematode

When DNA replication stops, the protein responsible for detecting replication pressure inactivates the CDK1 protein, which quickly stops cell division.

Cancer protection

Next, the research team began to investigate whether mammalian cells might have the same cell extrusion.
It was found that in mammals, cell extrusion plays an important role in replacing the lining cells of the intestines, lungs and other organs.

The research team used a chemical called hydroxyurea to induce DNA replication pressure in canine kidney cells growing in a petri dish, and found that this treatment increased the cell extrusion rate by a factor of three.

The study also found that in mammalian cells, the well-known cancer suppressor p53 is involved in initiating the extrusion of cells experiencing replication pressure.
This indicates that in addition to the known cancer protection effects of p53, it can also play a protective role by squeezing out cancerous cells or precancerous cells.

Replication pressure is one of the characteristics of precancerous cells or cancerous cells.
These findings indicate that crowding out cells under replication pressure may be a tumor suppressor mechanism.

From low-level sponges to high-level mammals, cell squeezing can be observed.
Moreover, this mechanism of clearing cells through cell squeezing only relies on the cell cycle and does not require special mechanisms like apoptosis.
To execute.
Therefore, the research team speculated that it may be a very early form of cell clearance, which was later replaced by programmed cell death involving apoptosis.

In general, the study found that when cells are unable to replicate their DNA during cell division, the process of cell extrusion is triggered, and confirmed that this mechanism is widespread in animals.
This mechanism may be biological clearance.
A primitive way of cancer cells or precancerous cells brings a whole new way of thinking about cancer treatment.

Original source:

Dwivedi, VK, Pardo-Pastor, C.
, Droste, R.
et al.
Replication stress promotes cell elimination by extrusion.
Nature (2021).
https://doi.
org/10.
1038/s41586-021-03526-y.