Molecular mechanisms of activated osteoblast-induced myeloma death through mitochondrial impairment and metabolic perturbation

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18420
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokushima
• Principal Investigator: NAKAMURA Shingen 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (10511321)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: multiple myeloma / osteoblast / Pim-2 / PGC-1α / AMPK

Outline of Final Research Achievements

In contrast to bone marrow stromal cells or osteoclasts, mature osteoblasts (OBs) induced myeloma (MM) cell death in parallel with downregulation of the pro-survival mediator Pim-2. The Pim-2 reduction triggered the downregulation of PGC-1α, an activator of glycolysis and mitochondrial biogenesis, along with subsequent ATP reduction and phosphorylation of AMPK, a key energy sensor, in MM cells. The AMPK inhibitor dorsomorphin mitigated MM cell death in cocultures with OBs. Therefore, the prompt reduction of Pim-2 and thereby PGC-1α suppression and AMPK activation in MM cells are suggested to cause the mature OB-triggered MM cell death with energy crisis.

Free Research Field

がん薬物療法学