Wang and McNiven reveal how a matrix metalloproteinase (MMP) is recruited to focal adhesions, where it degrades the extracellular matrix (ECM) to promote tumor cell invasion.
Cancer cells are thought to invade through tissues by forming invadopodia—actin-rich membrane protrusions that project from the base of the cell and contain MMPs that degrade the surrounding ECM. Invadopodia are formed by many of the same proteins that assemble into focal adhesions, which attach to the ECM and aid cell migration but aren't thought to function in matrix degradation. Wang and McNiven, however, noticed that many tumor cell lines degraded the matrix underlying both their invadopodia and their focal adhesions.
Matrix degradation by focal adhesions depended on a transmembrane MMP called MT1. This protease was recruited to focal adhesions because its cytoplasmic tail—when phosphorylated by the tyrosine kinase Src—bound to a protein called p130Cas, which bound, in turn, to the focal adhesion kinase (FAK). Cells lacking p130Cas or FAK couldn't degrade the matrix around their focal adhesions and invaded through ECM more slowly than control tumor cells, even though they still formed invadopodia.
Senior author Mark McNiven thinks that this degradative function for focal adhesions makes sense as they could cluster at the leading edge of invading cells to clear a path through the ECM. He thinks that researchers should continue to observe the invasive structures formed by tumor cells in vivo, where focal adhesions and invadopodia may interconvert due to the large number of components they have in common.
