Dr. Maddy Parsons. Fascin-dependent regulation of cell adhesion
Date: 4 February 2015 Time: 15:00 - 17:00
Fascin is an actin-binding and bundling protein that is highly upregulated in most epithelial cancers and strongly correlates with poor patient prognosis. Fascin localizes to filopodia and promotes cell migration in vitro and tumour cell metastasis in vivo. We have previously shown that depletion of fascin results in reduced focal adhesion dynamics through an unknown mechanism. We now demonstrate that fascin is required for microtubule-dependent focal adhesion disassembly and this is controlled independently of the well-characterized fascin-actin binding site around serine39. Mechanistically we show that fascin can directly interact with microtubules independently of actin-bundling and that this association promotes fascin positioning at the cell periphery and microtubule-dependent adhesion turnover. Moreover, fascin is also found in a complex with focal adhesion kinase (FAK), and this depends on dynamic microtubules. This data demonstrates a previously unappreciated role for fascin in control of microtubule stability and may have significant implications for the rational design of therapies to target fascin in metastatic disease.
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