What the mechanical forces behind protein folding can tell us about metastatic cancer

Talin is a protein that controls cellular attachment and movement, but its malfunctioning also allows cancer cells to spread. DCL1 is a tumor-suppressing protein. But scientists don’t fully understand how either protein works — or what happens when they don’t work the way they should.

One thing scientists doknow: When it is present in a cell, DCL1 can interact with talin and perhaps interfere with talin’s ability to group cells together. If scientists knew the exact steps in the process, they may be able to identify a treatment option to keep cancer from metastasizing.

To find answers, a team of researchers from the University of Wisconsin-Milwaukee used a unique tool that they built to apply the exact mechanical forces that act on talin in the body, beginning a process called protein unfolding that is necessary for the protein to perform its function.

With the tool, called “single molecule magnetic tweezers,” the scientists measured intracellular mechanical forces and experimented with them in the lab so that they can find what happens to talin when DCL1 is both present and not present in the cell.

They have discovered a unique behavior of talin, induced by mechanical forces, that demonstrates a strong interaction that can explain the antitumor effect of DLC1 when the two proteins bind.

“We still don’t know exactly what goes wrong with talin functioning when cancer cells metastasize,” said Ionel Popa, a UWM physics professor who led the team. “But it looks like talin plays a role in activating the spread of cells when the tumor-suppressing DCL1 is missing. And when DCL1 binds to talin, it appears to block talin from activating cell-spreading.”

The work is published today in the journal Science Advances.

Source: Read Full Article