Cells communicate with themselves and with their cellular environment through mechanical links. Now new research has advanced our understanding of the role of these forces on proteins as they interact to fulfill their biological functions, including cancer control.
The talin is a protein that controls cell adhesion and movement, but its malfunction also allows the spread of cancer cells. DCL1 is a tumor suppressor protein, but scientists don’t fully understand how either protein works, or what happens when they don’t work the way they should.
Scientists know that when present in a cell, DCL1 can interact with talin and perhaps interfere with its ability to clump cells together, but if they knew the exact steps in the process they could identify a treatment option to prevent cancer metastasize.
Unique Talin Behavior
They have discovered a unique behavior of talin, induced by mechanical forces, which demonstrates a strong interaction that may explain the antitumor effect of DLC1 when the two proteins bind.
Like all proteins, talin has a specific three-dimensional shape that defines its function. This process, known as protein folding, is one of the most complex in nature, and when it folds incorrectly, it often leads to disease. Popa’s lab investigates the forces that affect protein folding, which may lead to new treatments for diseases that begin when proteins misfold.
For some proteins, such as talin, mechanical forces inside and outside the cell are necessary for the protein to obtain the shape that unlocks its function. Inside cells, mechanical forces cause talin to unfold, exposing receptors to which other proteins can bind to form the necessary messenger connections.
The talin activation during cell propagation and the construction of tissues is controlled by hormones. In this stage, the protein undergoes cycles of stretching and binding with other proteins. Mechanical forces come into play as more proteins join the process.
For talin to become activated, it must be carried to the cell membrane by messengers that send signals from the cell’s cytoskeleton to the extracellular matrix, the environment in which cells are embedded.
Popa’s team tracked the effect of DCL1 on this process. “During this hormone-driven ‘inside-out’ activation, if DLC1 also binds talin, it will not allow this recruitment to the membrane –he points out–. Any of the steps that control cell propagation could be hijacked by cancer cells to become metastatic. In some cases, DLC1 is completely suppressed.”
The lack or malfunction of DCL1 may not be the only factor in the spread of cancer, Popa points out, but the work illustrates the alternative behaviors of proteins subjected to force and points to a direction to further study this protein interaction as a possible target of anticancer drugs.
–
