Targeting the pro-survival protein MET with tivantinib (ARQ 197) inhibits growth of multiple myeloma cells.

ABSTRACT: The hepatocyte growth factor (HGF)/MNNG HOS transforming gene (MET) pathway regulates cell growth, survival, and migration. MET is mutated or amplified in several malignancies. In myeloma, MET is not mutated, but patients have high plasma concentrations of HGF, high levels of MET expression, and gene copy number, which are associated with poor prognosis and advanced disease. Our previous studies demonstrated that MET is critical for myeloma cell survival and its knockdown induces apoptosis. In our current study, we tested tivantinib (ARQ 197), a small-molecule pharmacological MET inhibitor. At clinically achievable concentrations, tivantinib induced apoptosis by >50% in all 12 human myeloma cell lines tested. This biologic response was associated with down-regulation of MET signaling and i

SUBMITTER: Zaman S 

PROVIDER: S-EPMC4372650 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature