Analysis of the mechanism activating AKT signaling pathyway in melanoma cells by Interferon-gamma stimulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 26860895
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: Tanese Keiji 慶應義塾大学, 医学部(信濃町), 助教 (70464815)
• Research Collaborator: SAKAMOTO Michiie ; Ekmekcioglu Suhendan
• Project Period (FY): 2014-04-01 – 2018-03-31
• 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

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.

Free Research Field

悪性腫瘍