Stem cells can be large. Our bodies rely on their ability to become other cell types. If it goes wrong, some of our most useful cells could be turned into cancer.
While investigating a pathway involved in stem cell differentiation, researchers at UC Santa Barbara found that instead of forming an assembly line or rigid structure, all the proteins coalesce into a liquid droplets. The team began to show how cells use this droplet to process and relay information, and how it might malfunction in cancer. Their results appear in a journal.
Max Wilson, an assistant professor in the Department of Molecular, Cellular, and Developmental Biology, said that the same processes that organize dew drops on a spiderweb are happening in the cells. It causes 100% of colorectal cancers when it goes wrong and is implicated in a lot of other cancers.
It's an important process.
A host of mechanisms guide a stem cell The Wnt pathway takes input from outside the cell and relays instructions to the nucleus. The stem cell is told by this that it's time to differentiate and what type of cell to become. Wilson explained that the Wnt pathway is involved in determining the fate of stem cells in almost all animals.
It's important that stem cells are differentiated during embryo development. Stem cells can be found in a number of areas of the body, such as our bones, skin, and intestines. The function of the tissues and organs is dependent on the pathways that differentiate them.
Wilson and his colleagues were interested in learning how the Wnt pathway was organized inside the cell. They focused on two proteins that seem to provide the scaffolding for the whole process.
The function follows form.
Understanding a molecule's structure is more important than its composition. The team fed the chemical makeup of the proteins to AlphaFold, a deep- learning software that was developed by the company.
The program returned a random pile of spaghetti, which was as close to an error message as the program could get.
It was suggested that the two companies may be working in a different way. The proteins could be functioning in a more fluid, dynamic way. They thought they might be forming oil droplets in salad dressing. To see was the only way to tell.
They added a fluorescent tag to all the major genes they knew were part of the Wnt pathway. They looked through the microscope to see the liquid droplets in the cell's cytoplasm.
A strange path.
Most of the Wnt pathway happens in this liquid droplets, which eventually sends a message to the nucleus telling the cell to differentiate. The stem cell becomes what it is because of the changes to the genes. Wilson described it as a tiny little liquid computer in the middle of the cell. Scientists had never seen the Wnt pathway in action before.
The group observed that the droplets formed next to the nucleus. The centrosome is where chromosomes are pulled apart when a cell splits. Wilson is still looking at this part of the path. He thinks it may be an anti-cancer strategy. It's possible to coordinate growth, form and differentiation in tissues. We are not sure yet.
The most important compounds in the creation of the droplet are Axin andAPC. The main players in the blob are the WntProteins. The -catenin is being processed by the droplets. The blob modifies it and returns it to the cell. There are many other roles within the body.
The team was surprised by the results of the simulation. The pathway is more efficient if it is concentrated in a droplet. The blob can be used as a reaction chamber.
The team tinkered with the ratio of the proteins in the droplets. Increasing the Axin caused a lot of small droplets to form throughout the cell. The initial droplets grew larger when theAPC was turned up. This part of the pathway is being investigated by the team.
The other proteins that behave this way are not the only ones. Wilson said that the stress granules and the nucleolus are examples of liquidProtein Condensers. We are just beginning to understand these so called 'liquid proteins'.
There is a connection between the cancer and the disease.
There is a link between colorectal cancer and the Wnt pathway. It takes about three days for intestinal cells to leave the body. Stem cells that reside in the lining of the scuplture replenish them. When a replacement is needed, the stem cell divides and one daughter becomes an idiosyncrasy.
The Wnt pathway can cause a cell to grow and spread without regard to its surroundings or the environment. Almost all of the people with colorectal cancer have a big chunk missing out of theirAPC genes.
The dynamics and structure of the Wnt blob seem to have been altered by altering the genes. The pathway seems to be more sensitive to issues with theAPC gene. The team is researching this aspect of the system.
There is a need for colorectal cancer treatment. There is no immunotherapy for it. There is no intervention except for Chemo.
The FDA doesn't approve drugs that target the Wnt pathway. Wilson said that it suggests we might have been thinking about the wrong thing. The idea of a liquid orchestrating the whole process may help us design new drugs and therapies.
The Wnt pathway is implicated in other cancer as well. The researchers are looking at how cancer changes the dynamics of droplets. There should be a list of possible targets for new therapies.
More information: Nucleation of the destruction complex on the centrosome accelerates degradation of β-catenin and regulates Wnt signal transmission, Proceedings of the National Academy of Sciences (2022). Journal information: Proceedings of the National Academy of Sciences
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