Src Family Kinases are Regulated in Multiple Myeloma Cells by Phosphatase of Regenerating Liver-3

摘要: Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual-specificity phosphatase that upregulated in various types cancers and related to poor prognosis aggressive tumor behavior. The expression level PRL-3 elevated response several antiapoptotic cytokines, including IL6, cancer cells from patients with multiple myeloma (MM) can promote survival migration. Here, it demonstrated activates Src kinase the IL6-dependent MM cell line INA-6. Inhibition by small-molecule inhibitor or shRNA resulted inactivation Src. In addition activation Src, also activated family (SFK) members LYN HCK INA-6 cells. Forced catalytically inactive mutant decreased these three SFK while total FYN remained elevated. Inhibitors increased sensitivity overexpressing through joint downregulation both Mcl-1. conclusion, protected against apoptosis dysregulating levels specific are important for IL6 signal transduction Eventually, this led Implications: This study suggests SFKs key mediators IL6-driven signaling events points as potential targets treatment MM. Mol Cancer Res; 15(1); 69–77. ©2016 AACR.