| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| 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.
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