The phosphatase of regenerating liver-3 (PRL-3) is important for IL-6-mediated survival of myeloma cells

Abstract

Multiple myeloma (MM) is a neoplastic proliferation of bone marrow plasma cells. PRL-3 is a phosphatase induced by interleukin (IL)-6 and other growth factors in MM cells and promotes MM-cell migration. PRL-3 has also been identified as a marker gene for a subgroup of patients with MM. In this study we found that forced expression of PRL-3 in the MM cell line INA-6 led to increased survival of cells that were depleted of IL-6. It also caused redistribution of cells in cell cycle, with an increased number of cells in G2M-phase. Furthermore, forced PRL-3 expression significantly increased phosphorylation of Signal transducer and activator of transcription (STAT) 3 both in the presence and the absence of IL-6. Knockdown of PRL-3 with shRNA reduced survival in MM cell line INA-6. A pharmacological inhibitor of PRL-3 reduced survival in the MM cell lines INA-6, ANBL-6, IH-1, OH-2 and RPMI8226. The inhibitor also reduced survival in 9 of 9 consecutive samples of purified primary myeloma cells. Treatment with the inhibitor down-regulated the anti-apoptotic protein Mcl-1 and led to activation of the intrinsic apoptotic pathway. Inhibition of PRL-3 also reduced IL-6-induced phosphorylation of STAT3. In conclusion, our study shows that PRL-3 is an important mediator of growth factor signaling in MM cells and hence possibly a good target for treatment of MM.

DOI: 10.18632/oncotarget.8422

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@inproceedings{Slrdahl2016ThePO, title={The phosphatase of regenerating liver-3 (PRL-3) is important for IL-6-mediated survival of myeloma cells}, author={Tobias Schmidt Sl\ordahl and Pegah Abdollahi and Esten N. Vandsemb and Christoph Rampa and Kristine Misund and Katarzyna Anna Baranowska and Marita Westhrin and Anders Waage and Torstein Baade R\o and Magne B\orset}, booktitle={Oncotarget}, year={2016} }