The functional involvement of PDPK1 in the pathophysiology of multiple myeloma

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KURODA JUNYA 京都府立医科大学, 医学(系)研究科(研究院), 教授 (70433258)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 多発性骨髄腫 / PDPK1 / RSK2 / miR-375 / エピジェネティックス

Outline of Final Research Achievements

This research identified that the constitutive activation of PDPK1/RSK2 signaling pathway is universal in multiple myeloma which is highly heterogenous in terms of their molecular abnormalities. We also identified that the activation of PDPK1/RSK2 signaling is present from the disease initiation phase to the end stage disease, indicating its functional involvement of both disease development and disease progression in multiple myeloma. Indeed, PDPK1/RSK2 regulates myeloma cell survival and proliferation. In addition, we discovered that the abnormal repression of miR-375 by epigenetic dysregulation, such as hypermethylation or hypoacetylation, underlies as the causative of PDPK1 over/expression and its auto-activation in myeloma cells. As the abnormal regulation of miR-375/PDPK1/RSK2 axis is the universally observed in myeloma patients of varied disease stages, novel strategies to manipulate miR-375/PDPK1/RSK2 axis is desired to be developed in future.

Free Research Field

造血器悪性腫瘍