Filopodia

a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell

has important roles in cell motility. However

the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study

we further demonstrate that PRR11 involves in filopodia formation

focal adhesion turnover and cell motility through ARP2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically

PRR11 recruited and co-localized with Arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably

PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185–200) abrogated the effect of filopodia formation. In addition

PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin β1 in the cell surface

whereas reduced the phosphorylation level of focal adhesion kinase (FAK

Y397

) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together

our findings indicate that PRR11 has critical roles in controlling filopodia formation

focal adhesion turnover and cell motility by recruiting ARP2/3 complex

thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells.