and in the presence of HGF. Control cell invasion was enhanced approx. 2-fold by the addition of HGF, and shRNA-a cells had significantly reduced the invasive capacity of TE-1 cells in the context of HGF stimulation (p < 0.01), whereas with border-line significance (p = 0.051) in non-stimulated cells (Fig. 4D). ShRNA-b, however, had no effect on the invasion of non-stimulated cells, whereas there was a strong trend (p = 0.054) towards inhibition of HGF-driven invasion of TE-1 cells (Fig. 4D). Cell migration requires a continuous cycle of protrusion, attachment, and traction at the leading edge that depends on the coordinated dynamics of the actin cytoskeleton and focal adhesions (25). Indeed, IdoA was found to have a role in cell attachment and spreading, as well as in cytoskeleton dynamics; shRNA-a cells exhibited an approx. 40% greater cell area compared to control shRNA cells (Fig. S2B), which was associated with an approx. 2-fold induction of p-FAK and total FAK as compared with control cells (Fig. 4E). Moreover, p-FAK appeared to be increased and more homogeneously distributed at the cell membrane as compared with control cells in shRNA-a and shRNA-b cells after 48 h of HGF stimulation in a wound scratch assay
