Analysis of the mechanism activating AKT signaling pathyway in melanoma cells by Interferon-gamma stimulation
| Project/Area Number |
26860895
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
Tanese Keiji 慶應義塾大学, 医学部(信濃町), 助教 (70464815)
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| Research Collaborator |
SAKAMOTO Michiie
Ekmekcioglu Suhendan
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性黒色腫 / CD74 / インターフェロンγ / MIF / 腫瘍微小周囲環境 / インターフェロンガンマ / AKTシグナル / IL-6 / IL-8 / AKT |
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| Outline of Final Research Achievements |
IFN-γ produced by immune cells has a crucial role in tumor immune surveillance; however, it has also been reported to be pro-tumorigenic. In the current study, we found that IFN-γ enhances the expression of CD74, which interacts with its ligand, macrophage migration inhibitory factor (MIF), and thereby activates the PI3K/AKT pathway in melanoma, promoting tumor survival. IFN-γ increased phosphorylation of AKT Ser473 and upregulated total cell surface expression of CD74 in human melanoma cell lines tested. Blockade of CD74-MIF interaction reduced AKT phosphorylation and expression of pro-tumorigenic molecules, including IL-6, IL-8, and BCL-2. Inhibition of CD74-MIF interaction significantly suppressed tumor growth in the presence of IFN-γ in our xenograft mouse model. In the further analysis of Stage III melanoma lymph node metastasis samples, cases expressing MIF showed worse prognosis. Thus, we conclude that IFN-γ promotes melanoma cell survival by regulating CD74-MIF signaling.
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma.2016
Author(s)
Ekmekcioglu S, Davies MA, Tanese K, Roszik J, Shin-Sim M, Bassett RL Jr, Milton DR, Woodman SE, Prieto VG, Gershenwald JE, Morton DL, Hoon DS, Grimm EA.
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Journal Title
Clinical Cancer Research
Volume: 22
Issue: 12
Pages: 3016-30
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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