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

Research Project

Project/Area Number 26860895
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionKeio 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
Project Status Completed (Fiscal Year 2017)
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)
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
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.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (3 results)

  • [Int'l Joint Research] UT MD Anderson Cancer Center(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma2017

    • Author(s)
      Baba Yuko、Funakoshi T.、Mori M.、Emoto K.、Masugi Y.、Ekmekcioglu S.、Amagai M.、Tanese K.
    • Journal Title

      Journal of European academy of dermatology and venerology

      Volume: 31 Issue: 12 Pages: 2038-2045

    • DOI

      10.1111/jdv.14455

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lack of XAGE-1b and NY-ESO-1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients.2017

    • Author(s)
      Mori M,Funakoshi T,Kameyama K,Kawakami Y,Sato E,Nakayama E,Amagai M,Tanese K.
    • Journal Title

      J Dermatol.

      Volume: in press Issue: 6 Pages: 671-680

    • DOI

      10.1111/1346-8138.13730

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Clinical Cancer Research

      Volume: 22 Issue: 12 Pages: 3016-30

    • DOI

      10.1158/1078-0432.ccr-15-2226

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Two cases of atretic cephalocele, and histological evaluation of skin appendages in the surrounding skin.2016

    • Author(s)
      Fukuyama M, Tanese K, Yasuda F, Hayashi Y, Tanikawa A.
    • Journal Title

      Clin Exp Dermatol

      Volume: 41 Issue: 7 Pages: 48-52

    • DOI

      10.1111/1346-8138.12869

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ.2015

    • Author(s)
      Tanese K, Hashimoto Y, Berkova Z, Wang Y, Samaniego F, Lee JE, Ekmekcioglu S, Grimm EA.
    • Journal Title

      J Invest Dermatol

      Volume: 135 Issue: 11 Pages: 2775-84

    • DOI

      10.1038/jid.2015.204

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Metastatic eccrine porocarcinoma successfully treated with carboplatin and epirubicin chemotherapy.2015

    • Author(s)
      Fukuda K, Funakoshi T, Fukuyama M, Kakuta R, Sato M, Nakamura Y, Tanese K, Masugi Y, Amagai M.
    • Journal Title

      J Dermatol

      Volume: 42 Issue: 9 Pages: 928-30

    • DOI

      10.1111/1346-8138.12977

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Postherpetic Wolf's isotopic response: possible contribution of resident memory T cells to the pathogenesis of lichenoid reaction.2015

    • Author(s)
      Ise M, Tanese K, Adachi T, Du W, Amagai M, Ohyama M.
    • Journal Title

      Br J Dermatol

      Volume: 173 Issue: 5 Pages: 1331-4

    • DOI

      10.1111/bjd.13968

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Case of primary cutaneous adenoid cystic carcinoma: Expression of c-KIT and activation of its downstream signaling molecules.2015

    • Author(s)
      Matsumoto N, Hata Y, Tanese K.
    • Journal Title

      J Dermatol

      Volume: 42 Issue: 11 Pages: 1109-11

    • DOI

      10.1111/1346-8138.13054

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Case of syringomatous carcinoma: Positive immunohistochemical staining of c-KIT and phosphorylated-extracellular signal-regulated kinase 1/2.2015

    • Author(s)
      Ohi Y, Kosuge H, Tanese K.
    • Journal Title

      J Dermatol.

      Volume: 42 Issue: 12 Pages: 1191-2

    • DOI

      10.1111/1346-8138.13080

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.2015

    • Author(s)
      Masugi Y, Tanese K, Emoto K, Yamazaki K, Effendi K, Funakoshi T, Mori M, Sakamoto M.
    • Journal Title

      Pathol Int

      Volume: 65 Pages: 627-34

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 悪性黒色腫における癌精巣抗原の発現とその機能的役割の検討2015

    • Author(s)
      種瀬啓士
    • Organizer
      第74回日本癌学会
    • Place of Presentation
      名古屋国際会議場(名古屋市熱田区)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] インターフェロンγの刺激に対してメラノーマ細胞が示す生存応答機序の検討2015

    • Author(s)
      種瀬啓士
    • Organizer
      第31日本皮膚悪性腫瘍学会
    • Place of Presentation
      大阪国際会議場(大阪市北区)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
  • [Presentation] Cell surface CD74 expression is a key mediator of melanoma cell survival in response to the cytotoxic effect of interferon-gamma2014

    • Author(s)
      種瀬啓士
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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