Abstract Introduction It was demonstrated that metallopanstimulin-1 (MPS-1, RPS27) inhibited the growth of tumors formed by head and neck squamous cell carcinoma cells and reduced paxillin gene expression. Methods The present study examined whether and how MPS-1 affects another type of cancer, multiple myeloma (CAG). Enhanced expression of MPS-1 dramatically inhibited CAG in vitro and in vivo. Results Overexpression of MPS-1 resulted in decreased fibroblast growth factor (FGF2) receptor 3 and impaired endogenous MAPK/ErK signaling. MAPK/ErK signaling was not stimulated by adding recombinant FGF2 to myeloma cells overexpressing MPS-1. Conclusions These data suggest that MPS-1 suppresses CAG growth and that weakened FGF2 signaling may contribute to this effect.