A new mechanism in cell communication that promotes cancer metastasis

Communication between cells is key to the coordinated functioning of organs, and a breakdown in communication is one of the characteristic features of cancer and chronic inflammatory diseases. Traditionally, such loss of communication between cells had been understood to result from purely biochemical reasons, such as hormones. Recently, however, the Integrative Cell and Tissue Dynamics group led by Xavier Trepat, ICREA researcher at IBEC, has challenged this traditional view, showing that the physics of communication between cells is as important as the chemistry behind it. “Because the cells in our tissues are in physical contact, we’ve always suspected that communication through physical forces may be faster and efficient than through the purely biochemical mechanisms that are described in textbooks,” says Xavier.

In the study, the group – together with colleagues at the Technical University of Catalonia (UPC) and the Rovira i Virgili University (URV) – combined molecular biology, nanotechnology and mathematical models to not only identify the molecules involved in the physical communication between cells, but also to show that some of these molecules are altered in various cancers. “We expected to find a single protein responsible for the transmission of forces between cells, and we found a dozen,” says Xavier.

The mechanisms they’ve discovered open new possibilities for the control of metastasis, but what has surprised researchers has been discovering how these proteins work together. “Our analysis suggests that proteins control cell force in a very similar way to the way modern electronic systems control appliances – that is, using what engineers call proportional-integral-derivative controller (PID controller) systems,” explains Xavier. “This shows that cells developed advanced control systems million of years before we did!”

The next step in the group’s research will be explore these control mechanisms further and study how alterations in the mechanisms promote metastasis, with the ultimate goal of being able to redirect these changes to affect behavior differently. “We are faced with very complex scenarios,” says Xavier. “It’s not just a case of changing the levels of a single protein. A great many proteins are involved, working together in ways that could be complementary – or just as likely, competing with each other.”

This study, which was supported by the Obra Social “la Caixa”‘s pilot initiative to fund research evaluation and technology transfer, has received funding from national and European agencies such as the European Research Council (ERC).

Reference article: Elsa Bazellières, Vito Conte, Alberto Elosegui-Artola, Xavier Serra-Picamal, María Bintanel-Morcillo, Pere Roca-Cusachs, José J. Muñoz, Marta Sales-Pardo, Roger Guimerà and Xavier Trepat (2015). Control of cell-cell forces and collective cell dynamics by the intercellular adhesome. Nature Cell Biology, 17, 409–420

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