An international research team reports that the cytoskeleton can trigger the multiplication of cells through the action of proteins that control cellular rigidity. During this process oncogenes become activated, leading to tumor formation in living organisms.
The study (“Zyxin antagonizes the FERM protein Expanded to couple F-actin and Yorkie-dependent organ growth”) is published in Current Biology.
The cytoskeleton, which is composed of a mesh of filaments made of protein, confers the shape of the cell, helps cells moving, and also works as a pathway that proteins use to move inside the cell and perform their job. Scientists have been studying the different roles of the cytoskeleton, but only recent studies carried out in cultured cells suggest that mechanical forces could impact on how the cytoskeleton is organized and lead to the proliferation of cells.
Florence Janody, Ph.D., principal investigator at the Instituto Gulbenkian de Ciência in Portugal and her team took a step forward and have now shown that proteins of the cytoskeleton, which control mechanical forces, can induce the activation of factors that promote tumor growth in a living organism (Drosophila melanogaster). Her group observed that when the dynamics of the cell's skeleton changes, this leads to different rearrangements in the mesh of filaments, which can have direct consequences on cell proliferation and tissue overgrowth. If the cytoskeleton becomes less elastic, the cells proliferate faster.
Using both genetic and molecular approaches, the researchers identified a protein important for this process, Zyxin, which controls the “correct” assembly of the cytoskeleton to allow cell's normal function. If Zyxin does not work properly, it compromises the cytoskeleton’s organization, unleashing the function of other proteins that ultimately lead to uncontrolled cell proliferation and tumor development.
“The cell's skeleton was [identified] more than 150 years ago as the cellular structure allowing muscles to create forces. We came to realize only recently that mechanical forces generated by the cell's skeleton dictate the behavior of all cells of the body. The next challenge will be to identify the large diversity of mesh of skeleton filaments built in the cells and characterize their mechanical properties,” said Dr. Janody.
The team believes their findings will shed light on the specific manner in which mechanical forces are relayed through the cytoskeleton and how they affect cellular proliferation. They also hope that these new perspectives suggest novel approaches to tumor therapy and regenerative medicine.