Pim-2 Kinase Regulates Energy Metabolism in Multiple Myeloma

Abstract

Pim-2 kinase is overexpressed in multiple myeloma (MM) and is associated with poor prognosis in patients with MM. Changes in quantitative metabolism, glycolysis, and oxidative phosphorylation pathways are reportedly markers of all tumor cells. However, the relationship between Pim-2 and glycolysis in MM cells remains unclear. In the present study, we explored the relationship between Pim-2 and glycolysis. We found that Pim-2 inhibitors inhibited glycolysis and energy production in MM cells. Inhibition of Pim-2 decreased the proliferation of MM tumor cells and increased their susceptibility to apoptosis. Our data suggest that reduced Pim-2 expression inhibits the energy metabolism process in MM, thereby inhibiting tumor progression. Hence, Pim-2 is a potential metabolic target for MM treatment.

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

“…This overexpression is attributed to the interplay of transcriptional activation and positive feedback loop stabilization mechanisms involving upstream regulators, including JAK/STAT, PI3K/AKT, and NF-κB signaling pathways. 33 The transcriptional activation of PIM kinases is facilitated by various interleukins and receptors, including IL-2, IL-3, IL-5, IL-6, IL-7, IL-12, IL-15, GM-CSF, PRL, EGFR, TNF-α, and INF-γ. 34 PIM kinases regulate multiple substrates by phosphorylation in cells, thereby affecting a variety of cellular processes, including senescence, apoptosis, cell migration and invasion, as well as cell proliferation and protein translational metabolism.…”

“…PIM kinases are enzymes that exhibit constitutive activity and are frequently overexpressed in cancer cells. This overexpression is attributed to the interplay of transcriptional activation and positive feedback loop stabilization mechanisms involving upstream regulators, including JAK/STAT, PI3K/AKT, and NF-κB signaling pathways . The transcriptional activation of PIM kinases is facilitated by various interleukins and receptors, including IL-2, IL-3, IL-5, IL-6, IL-7, IL-12, IL-15, GM-CSF, PRL, EGFR, TNF-α, and INF-γ .…”

PIM Kinases as Potential Biomarkers and Therapeutic Targets in Inflammatory Arthritides

“…The role of these proteins in non-cancer cells is not yet fully clarified; however, their ability to regulate many cellular functions has been highlighted [ 13 ]. As for the involvement of PIMs in the immune response and inflammation, PIM kinases stimulate the survival of T and B lymphocytes, induce the differentiation of T lymphocytes in the different subtypes Th1 and Th2, activate the natural killer cells, and regulate the immunosuppressive function of Treg cells [ 14 ]. IL-6, IL-17, IL-1β, TNF-α, and IFN-γ are among the cytokines mainly involved in these functions [ 3 , 4 , 15 , 16 ].…”

An overview of pim kinase as a target in multiple myeloma

“…Tumor load, bone disease, and immunity are the three fundamental issues that have drawn clinical attention in MM. The family of pim kinases comprises three isozymes: pim‐1, pim‐2, and pim‐3, all of which are reported to be overexpressed in several hematologic malignancies 1 . Several pathways and molecules involved in tumor progression, such as the well‐known interleukin (IL)‐6/STAT3 and TNF/NF‐κB pathways, have recently been found to be involved in the transcription of pim kinases as well 2 .…”

“…The family of pim kinases comprises three isozymes: pim‐1, pim‐2, and pim‐3, all of which are reported to be overexpressed in several hematologic malignancies. 1 Several pathways and molecules involved in tumor progression, such as the well‐known interleukin (IL)‐6/STAT3 and TNF/NF‐κB pathways, have recently been found to be involved in the transcription of pim kinases as well. 2 Targeting these pathways would inhibit myeloma cell proliferation by promoting cell cycle arrest and activating metabolic pathways, such as glycolysis and lipid biosynthesis.…”