Sep. 21, 2009 The adhesion of cells to the various components of their environment is mediated mainly by molecules known as integrins. Two integrins, α5β1 and αvβ3, mediate adhesion with fibronectin, which is present in the extracellular matrix. But why are two molecules involved in the adhesion to a single extracellular component?
An article published on-line in Proceedings of the National Academy of Sciences (PNAS), whose main author is Pere Roca-Cusachs, an IBEC researcher, offers the first experimental answer to this question.
The article shows the functional difference between the two integrins, as well as their complementarity. The integrin α5β1 is responsible for resisting the forces of the cellular environment while at the same time maintaining the integrity of the bond between the cell and its environment. The integrin αvβ3, on the other hand, merely detects such forces, without exerting any additional resistance. This discovery also confirms the intuitive idea that the cell is like a microscopic machine with a capacity for detection and resistance with which it relates to its environment.
The study was carried out with fibroblasts. Specifically, we studied the adhesion of the two integrins with fibronectin, a protein that is essential for cellular adhesion, wound healing, and embryogenesis. The communication of the cell with its environment is also an important factor in the development of tumors, as an increase in tissue rigidity is one of the first changes detected in a tumor. As the environment becomes more rigid, the behavior of the cell can be transformed from normal to cancerous.
Anti-cancer therapies based on the inhibition of integrins are currently available, and an understanding of the mechanisms by which integrins affect the response of tissue cells is essential in order to develop drugs that are more specific and that have fewer secondary effects. The identification of integrin αvβ3 as a detector of forces makes it a candidate for consideration in the development of anticancer therapies, as its role can account for some of the malignant behavior of tumors associated with changes in rigidity.
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- Pere Roca-Cusachs, Nils C. Gauthier, Armando del Río, and Michael P. Sheetz. Clustering of α5β1 integrins determines adhesion strength whereas αvβ3 and talin enable mechanotransduction. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0902818106
Note: If no author is given, the source is cited instead.