Adhesion Protein Plays Double Agent, Key Role in Cell Migration

    If you’ve ever been on the receiving end of a good pinch, you’re probably well aware of how much they can hurt, but perhaps a little less cognizant of the molecular mechanisms that prevent your skin detaching from the body. The mechanics at the cellular level that provide this protection are not only fascinating, but integral for cell adhesion, tissue development, and possibly even tumor invasion.

    Now, scientists from the Barcelona Institute for Research in Biomedicine (IRB Barcelona) have revealed a new function for the cell adhesion protein called E-cadherin (E-Cad) that typically keeps cells tightly bound together. This new E-Cad role sharply contrasts its previously accepted function for impeding cell movement, and the investigators found that it has a critical function in coordinating cell movement in diverse tissue types.

    While studying the development of the digestive system in the fruit fly Drosophila melanogaster, the IRB researchers observed that E-Cad facilitated the movement of heterogeneous groups of cells in a coordinated manner. Once the cells were at their destination and begin to distribute, their moderate levels of E-Cad kept them bound together, but not immobile. This new function of E-Cad may explain why tumors that express intermediary levels of this protein have a poorer prognosis.

    “Cell migration is a common and necessary process for an embryo and also for the correct function of the adult organism. What has been most surprising is the observation that E-Cad is a key component in cell movement, when its role was previously assumed to be that of keeping cells static,” explains Jordi Casanova, Ph.D., group leader of the Development and Morphogenesis in Drosophila laboratory at IRB Barcelona.

    The findings from this study were published recently in Nature Communications through an article entitled “A role for E-cadherin in ensuring cohesive migration of a heterogeneous population of non-epithelial cells.”

    Additionally, cell migration is of great biomedical relevance, and research into this phenomenon is beginning to shed light on how, for example, cancer metastasis and other processes such as wound healing and inflammation arise. Dr. Casanova and his team point out that discrepancies in E-Cad levels have been shown previously to be strongly associated with aggressive tumor phenotypes.

    “The more we learn about metastases, the more evidence emerges that they are formed by groups of cells and not by individual ones,” Dr. Casanova noted. “A cell that migrates alone is much easier to eliminate than a group of cells with different functions.”

    The IRB team was excited by their novel findings and hope that further study will reveal new targets for therapeutic intervention.

    “These results indicate an active role for E-Cad in mediating cohesive and ordered migration of non-epithelial cells, and discount the notion of E-Cad as just an epithelial feature that has to be switched off to enable migration of mesenchymal cells,” the scientists conclude.