Tight Junction Protein 1 is a Modulator and Biomarker of Proteasome Inhibitor Sensitivity in Multiple Myeloma

ABSTRACT: Proteasome inhibitors are important chemotherapeutics in the treatment of multiple myeloma, but they are currently used empirically as no markers of sensitivity have been validated. We have identified expression of tight junction protein (TJP) 1 as being associated with sensitivity of plasma cells in vitro and in vivo to proteasome inhibitors. TJP1 suppressed expression of genes in the major histocompatibility class II region, including two catalytically active immunoproteasome subunits, thereby decreasing proteasome activity, a critical determinant of proteasome inhibitor sensitivity. This occurred through suppression by TJP1 of signaling through the epidermal growth factor receptor/Janus kinase 1/signal transducer and activator of transcription 3 pathway. In the clinic, high TJP1 exp

ORGANISM(S): Homo sapiens

SUBMITTER: Wencai Ma 

PROVIDER: E-GEOD-52369 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress