Elucidation of the molecular mechanism involved in dysregulation of PTEN phosphorylation and its physiological role in cancers
| Project/Area Number |
25430113
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | NDRG2 / PTEN / リン酸化修飾 / ATL / PI3K/AKT / 低酸素応答 / 阻害剤 / SCYL2 / リン酸化 / 成人T細胞白血病 / AKT |
|---|
| Outline of Final Research Achievements |
NDRG2 is frequently down-regulated in various type of cancers including ATL. NDRG2 regulates PI3K/AKT pathway by dephosphorylation of PTEN via recruitment of PP2A. In this study, we found that NDRG2 acts as a novel negative feedback regulator in the PI3K/AKT pathway. PI3K-activated SGK1 phosphorylates NDRG2-Ser332 to promote PP2A binding to NDRG2 and dephosphorylation of PTEN, which plays a crucial role in the control of level of AKT activation. In addition, we identified Ser/Thr kinase SCYL2 as a novel PTEN interacting protein that functions in phosphorylation of PTEN-STT. SCYL2 expression is up-regulated in ATL cells and is essential for the enhanced PTEN-STT phosphorylation. As a potential physiological relevance of NDRG2 down-regulation, we demonstrated that NDRG2 inactivation renders ATL cells resistant to growth inhibition under hypoxic condition through sustained AKT activation, which may play a role in ATL development and progression.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer.2014
Author(s)
5.Nagai K, Nakahata S, Shimosaki S, Tamura T, Kondo Y, Baba T, Taki T, Taniwaki M, Kurosawa G, Sudo Y, Okada S, Sakoda S, Morishita K
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Journal Title
Cancer Med.
Volume: 3
Issue: 4
Pages: 18-26
DOI
Related Report
Peer Reviewed
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[Journal Article] Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers.2014
Author(s)
Nakahata S, Ichikawa T, Maneesaay P, Saito Y, Nagai K, Tamura T, Manachai N, Yamakawa N, Hamasaki M, Kitabayashi I, Arai Y, Kanai Y, Taki T, Abe T, Kiyonari H, Shimoda K, Ohshima K, Horii A, Shima H, Taniwaki M, Yamaguchi R, Morishita K.
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Journal Title
Nat Commun
Volume: in press
Issue: 1
Pages: 3393-3393
DOI
Related Report
Peer Reviewed / Open Access
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