Cellular mechanism may change cancer treatment

Understanding how cancer spreads is critical to stopping it; lately, researchers have been making significant progress in this direction.

Using the latest imaging techniques, for example, scientists were able to see how cancer cells “surf” the bloodstream, penetrating through blood vessels to reach new destinations.

Other studies have shown how the loss of certain proteins causes cancer cells to change their shape, which helps them to escape the immune system.

Now, a new study zooms in on a cellular mechanism that enables cancer cells to divide and migrate. The research was conducted by an international team of scientists led by Steffen Scholpp, who is a professor and principal investigator at the University of Exeter in the United Kingdom.

Prof. Scholpp and colleagues are hopeful that their findings — which were published in the journal eLife — will help change treatment practices not only for cancer, but also for developmental disorders.

Signaling protein ensures its own transport

For an organism to develop normally, cells must be able to communicate, or send signals, to each other.

So-called Wnt proteins are vital for this developmental process. They control the proliferation of cells, so they are crucial for the development of embryos and organs.

In other words, Wnt signaling drives growth by enabling cells to divide. While growth is normally a good thing, when it comes to cancer, faulty Wnt signaling may cause the “wrong” cells to divide — the malignant ones.

The role of Wnt signaling in cancer has been documented thoroughly, first in colorectal cancer and then in other forms of the disease.

However, until now, the precise mechanism by which Wnt sends its signals was unknown. However, Prof. Scholpp and his colleagues found that certain protrusions, or “bumps,” on a cell are key for signal transmission — which, in turn, regulates the rate at which cells divide and multiply.

These cell bumps are called cytonemes, and they serve to “transport signaling proteins between signaling cells.”

Prof. Scholpp and team found that if they stop the cytonemes from forming, this “short-circuits” the signal transmission from Wnt-producing cells. They were also able to observe how Wnt moves across the cell membrane and interacts with a receptor so that it forms a cytoneme.

To the authors’ knowledge, this is the first time that a signaling protein such as Wnt has been found to create its own “transportation system.”

Toward new cytoneme-targeting treatments

The study’s senior investigator explains what the findings mean and how they revolutionize our understanding of cell biology.

“In the early days, researchers believed that signaling molecules are released from cells into the extracellular space, the area between cells, and diffuse randomly. This would mean that target cells are surrounded by a mix of various signaling molecules.”

“In contrast,” Prof. Scholpp continues, “our research shows that there is a flexible grid of tiny protrusions connecting all cells in a multicellular body. This novel concept allows a fast, precise, and controlled exchange of information between sender cells and target cells.”

“We have started to understand the characteristics of this information grid in the matrix of a tissue,” the researcher says, adding, “These are very exciting times for cell biology.”

Our research provides the first insight how this web of cell protrusions is formed and what kind of consequences it has if we alter these connections.”

Prof. Steffen Scholpp

Such alterations could lead to new cancer drugs that would work by stopping the formation of cytonemes.

Additionally, given the important role of Wnt signaling in embryo and organ development, as well as in cellular regeneration and wound healing, such drugs could also be used to treat other developmental conditions.

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