It has been reported that p21-activated kinase 4 (PAK4) is amplified in 
pancreatic cancer tissue. PAK4 is a member of the PAK family of serine/threonine 
kinases, which act as effectors for several small GTPases, and has been 
specifically identified to function downstream of HGF-mediated c-Met activation 
in a PI3K dependent manner. However, the functionality of PAK4 in pancreatic 
cancer and the contribution made by HGF signalling to pancreatic cancer cell 
motility remain to be elucidated. We now find that elevated PAK4 expression is 
coincident with increased expression levels of c-Met and the p85α subunit of 
PI3K. Furthermore, we demonstrate that pancreatic cancer cells have a specific 
motility response to HGF both in 2D and 3D physiomimetic organotypic assays; 
which can be suppressed by inhibition of PI3K. Significantly, we report a 
specific interaction between PAK4 and p85α and find that PAK4 deficient cells 
exhibit a reduction in Akt phosphorylation downstream of HGF signalling. These 
results implicate a novel role for PAK4 within the PI3K pathway via interaction 
with p85α. Thus, PAK4 could be an essential player in PDAC progression 
representing an interesting therapeutic opportunity.