Nadia Elkhatib, Marie Schoumacher, Danijela Vignjevic
 

Morphogenesis and Intracellular Signalling, Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 05, France

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In order to escape from the primary tumor and invade adjacent tissue, cancer cells degrade the basement membrane (BM) using invadopodia, specialized protrusions for matrix degradation. We found that the crossing of a native BM is a three-stage process: invadopodia form and perforate the BM, elongate into mature invadopodia, and then guide the cell towards the stromal compartment. We showed that invadopodia form by assembly of dendritic and bundled actin networks and then mature by elongation of actin bundles followed by entry of microtubules and vimentin filaments. Upon BM degradation cancer cell migrate towards the circulatory system by coordination of protrusion of the leading edge and translocation of the cell body. During directional cell migration an actin bundling protein, fascin, cycles between phosphorylated and unphosphorylated states. Our hypothesis is that non-phosphorylated fascin is required for filopodia formation and cell guidance while phosphorylated fascin is necessary for the turnover of focal adhesions (FAs) and cell body retraction. Using TIRF microscopy we found that GFP-tagged fascin was enriched in the FAs and that turnover of FAs was significantly decreased in the fascin-depleted cells. Only expression of phospho-mimetic fascin mutant, S39E, was able to rescue the phenotype, suggesting that phosphorylation of fascin have a role in the FAs turnover independently of its actin bundling role. I will discuss the possible mechanism of fascin role in FAs turnover.