Phosphatase of regenerating liver‐3 regulates cancer cell metabolism in multiple myeloma

Cancer cells often depend on microenvironment signals from molecules such as cytokines for proliferation and metabolic adaptations. PRL-3, a cytokine-induced oncogenic phosphatase, is highly expressed in multiple myeloma associated with poor outcome this cancer. We studied whether PRL-3 influences metabolism. Cells transduced to express had higher aerobic glycolytic rate, oxidative phosphorylation, ATP production than the control cells. promoted glucose uptake lactate excretion, enhanced levels of proteins regulating glycolysis enzymes serine/glycine synthesis pathway, side branch glycolysis. Moreover, mRNAs these correlated expression primary patient Glycine decarboxylase (GLDC) was most significantly induced metabolism gene. Forced GLDC downregulation partly counteracted PRL-3-induced glycolysis, indicating involvement PRL-3-driven Warburg effect. AMPK, HIF-1α, c-Myc, important regulators cancer cells, were not mediators PRL-3’s effects. A phosphatase-dead mutant, C104S, many changes by wild-type arguing that effects are independent its phosphatase activity. Through study, emerges one key adaptations myeloma.