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.
Filamins prevent cell invasion
Filamins prevent cell invasion. J Cell Sci 15 August 2012; 125 (16): e1606. doi:
Download citation file:
Advertisement
Cited by
Introducing our new Editors
We welcome three new Editors to Journal of Cell Science - Robert Parton, Richa Rikhy and Simon Cook. You can read more about them in the Editorial from our Editor-in-Chief Michael Way.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Final registration deadline: 3 May 2024.
Workshop: Physics of the Early Embryonic Cell Divisions
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 11-14 November 2024. Application deadline: 17 May.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.
Propose a new Workshop for 2026
We are now accepting proposals for our 2026 Workshops programme. We aim to be responsive to the community and open to novel initiatives, so if you have a new idea for a biological workshop that you feel would work well, please apply. Applications deadline: 19 July 2024.