2018 Fiscal Year Final Research Report
AKT signaling in control of ATL tumorigenicity; unveiled mechanism for its heterogenous activation among ATL cell populations
| Project/Area Number |
15K06848
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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 | Miyagi Prefectural Hospital Organization Miyagi Cancer Center |
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Principal Investigator |
Yamaguchi Kazunori 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん制御研究部, 上席主任研究員 (80373215)
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| Research Collaborator |
Sugamura Kazuo
Nasu Kentaro
Takanashi Tomoka
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | 成人T細胞白血病 / AKTシグナル |
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| Outline of Final Research Achievements |
Human retrovirus HTLV-1 is an etiological agent for Adult T-cell leukemia/lymphoma (ATL), but additional cellular events such as aberrant modulation of signal transduction taking place for several decades after the initial HTLV-1 infection are totally unveiled. Previously we obtained highly tumorigenic populations of ATL-derived ST1 and TL-Om1 cells and found these cell populations exhibited an activated AKT signaling pathway, which may contribute to the malignancy observed in the ATL-derived cells. In this study we analyzed molecular mechanism underlying upregulation of AKT signaling in the highly tumorigenic ATL cells and found that PIK3IP1 and INPP5D, negative regulators for AKT signaling, are both inactivated in these cells. In addition, our observations suggest that activating phosphorylation of AKT might be accomplished by atypical kinase(s) in ATL cells.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
HTLV-1ウイルス感染者は西日本を中心に数十万から百万人程度で、この内の５％程度がATLを発症すると推定されている。発症後の治療法として骨髄移植と抗ＣＣＲ４抗体治療が知られているが適用の年齢制限や抵抗性などの問題があり、新たな治療法の開発が望まれている。本研究はATL悪性化の一因としてAKTシグナル伝達系の活性化に着目し、その分子機構の解明を試みたもので、その成果は新たな治療戦略への寄与が期待される。
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