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Filamins prevent cell invasion

Filamins are actin-binding proteins that not only bundle actin filaments but also connect different membrane-spanning proteins, including adhesion and signalling receptors, to the actin cytoskeleton and serve as a scaffold for intracellular signalling proteins. Deficiency of filamin A (FLNA, the most abundant filamin) is associated with migration defects in melanoma and neuronal cells, but has also been shown to enhance breast cancer invasiveness. Here, David Calderwood and co-workers (p. 3858) now demonstrate that FLNA has a role in extracellular matrix (ECM) remodelling and, consequently, is involved in regulating tumour cell invasion. They show that FLNA knockdown in fibrosarcoma cells leads to an increase in matrix metalloproteinase activity compared with that in wild-type cells. As a result, cells lacking FLNA have an enhanced ability to degrade and invade gelatin and fibronectin matrices. FLNA knockdown decreases tissue inhibitor of metalloproteinase 2 (TIMP2) secretion, which results in enhanced matrix metalloproteinase 2 (MMP2) activation. By using a trans-well migration assay, the researchers also show that the lack of FLNA does not affect regular cell motility but enhances cell invasion into a three-dimensional matrix. Taken together, these findings illustrate that filamin has an important role in ECM remodelling and cell invasion.