MK2 Is a Therapeutic Target for High-Risk Multiple Myeloma

p38 mitogen-activated protein kinase (MAPK) is constitutively activated in human multiple myeloma (MM). However, a major substrate of p38, MAPKAPK2 (MK2) has received little attention in MM. In this study, we disclosed that elevation of MK2 on DNA, mRNA and protein levels in MM cells compared to normal plasma control cells by array-based comparative genomic hybridization (aCGH), Gene expression profiling (GEP) and immunohistochemistry (IHC) respectively. High MK2 expression prognosticated inferior outcome of newly diagnosed myelomas, particularly in patients with high-risk disease based on GEP. Follow-up study demonstrated that enforced overexpressing MK2 promoted MM cell proliferation, drug-resistance and xenograft tumorigenesis in vivo, while knockdown MK2 expression by shRNA abrogated these characteristics. Further mechanism study showed MK2 directly bound and activated AKT signaling in MM, while specific MK2 inhibitor inhibited MM cell growth and clonogenicity through suppressing AKT phosphorylation. Our findings not only indicate that MK2 is a potential therapeutic target in high-risk MM but also suggest the clinical relevance of MK2 inhibition in MM.