P0017 S100P regulates cytoskeleton dynamics to promote cell migration and metastasis

Background S100P is an EF-hand calcium-binding protein. Like S100A4 and S100A6, S100P is expressed at a high level in cancers, particularly in those of the prostate, pancreas, and breast. We have demonstrated that S100P is a metastasis-inducing protein and that its upregulation enhances cell migration. When studying the molecular mechanisms, we found that S100P interacts separately with two major components of cytoskeleton, non-muscle myosin IIA (NMIIA) and tubulin. The aim of this study was to understand how S100P enhances cell migration through these protein interactions. Methods S100P-inducible cell lines and specific siRNAs were used to control the expression of S100P in cells. We used specific chemicals to disrupt actin stress fibres and microtubules and peptides to block the protein interactions. Results S100P differentially regulates NMIIA and NMIIB filaments, which reduced cell adhesion and enhanced cell migration. This process involves Rho, RAC1, and focal adhesion kinase. S100P upregulation simultaneously altered the dynamics of tubulin polymerisation to facilitate cell migration. Interpretation S100P directly regulates the dynamics of both actin-myosin filaments and microtubules, and the co-regulation of these cytoskeletons may synergistically enhance cell migration and promote cancer cell metastasis.