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| Invited Talk, Friday, 17:30 – 18:00 |
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| Role of fascin in invadopodia
formation and turnover of focal adhesions
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. |
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