HepG2.2.15 as a model for studying cell protrusion and migration regulated by S100 proteins

•Seven S100 family members were almost totally undetectable in HepG2.2.15 cells.•S100 proteins rescue the defects in protrusion and migration of HepG2.2.15 cells.•S100 proteins promoted actin polymerization.•S100A10 may interact with β-actin, β-tubulin and annexin A2 protein.•Promotion of cell protrusion by S100A10 was dependent on Cdc42 activation. Much of the difficulty in elucidating the precise function of S100 protein family has been attributed to functional redundancy and compensation by its conserved family members. In this study, we showed that seven S100 family members were almost totally undetectable in HepG2.2.15 cells, while all of them were highly expressed in its parental HepG2 cells. Re-expression of S100 proteins in HepG2.2.15 cells can partially rescue their defects in cell protrusion and migration through the regulation of cytoskeletons and adhesions. Thus, HepG2.2.15 can serve as a useful model for studying cell protrusion and migration regulated by S100 proteins.