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Notch signaing promotes proliferation and migration of melanoma.

Research Project

Project/Area Number 25461689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionShinshu University

Principal Investigator

KINIWA Yukiko  信州大学, 学術研究院医学系(医学部附属病院), 講師 (20436893)

Co-Investigator(Kenkyū-buntansha) OKUYAMA Ryuhei  信州大学, 学術研究院医学系, 教授 (80292332)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメラノーマ / Notchシグナル / DELTA-like 3 / MAPK経路 / Notchシグナリング / Notchリガンド
Outline of Final Research Achievements

Background: Notch signaling is crucial for development and cell differentiation in various tissues. It is also elucidated to be important in tumorigenesis. There are four Notch receptors (Notch1~4) and five ligands [Delta-like (DLL) 1/3/4 and Jagged 1/2] in Notch signaling pathway. Notch1 has been reported to be oncogenic in melanoma. However, little is known about importance of the ligands. In this study, we tried to determine the role of DLL3 in progression of melanoma.
Results: DLL3 was preferentially expressed in melanoma rather than melanocytic nevus. HES1 expression was decreased by DLL3-knockdown using specific siRNA, showing that DLL3 contributes to Notch signaling pathway. DLL3-knockdown decreased cell proliferation and migration. DLL3-knockdown led G0/G1 arrest, and suppressed MAPK signaling pathway. DLL3 overexpression increased cell proliferation and migration. These findings provided insight into the role of DLL3 in melanoma progression through MAPK activation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] 5-hydroxymethylcytosine as a useful marker to differentiate between malignant melanomas and benign melanocytic nevi2014

    • Author(s)
      Uchiyama R, Uhar H, Uchiyama A, Ogawa E, Takazawa Y, Ashida A, Koga H, Hayashi K, Kiniwa Y, Okuyama R
    • Journal Title

      J Dermatol Sci

      Volume: 73 Issue: 2 Pages: 161-163

    • DOI

      10.1016/j.jdermsci.2013.09.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 悪性黒色腫の浸潤・転移(2)浸潤・転移に関連する非免疫機序2013

    • Author(s)
      木庭幸子
    • Journal Title

      日本臨床

      Volume: 71 増4 Pages: 171-175

    • Related Report
      2013 Research-status Report
  • [Journal Article] 悪性黒色腫の循環腫瘍細胞2013

    • Author(s)
      上條史尚、木庭幸子、宇原久、奥山隆平
    • Journal Title

      日本臨床

      Volume: 71 増4 Pages: 93-97

    • Related Report
      2013 Research-status Report
  • [Journal Article] MAPキナーゼ:NRAS、BRAF、MEK2013

    • Author(s)
      芦田敦子、木庭幸子、宇原久、奥山隆平
    • Journal Title

      Int J Clin Oncol

      Volume: 71 増4 Pages: 126-129

    • Related Report
      2013 Research-status Report
  • [Presentation] DELTA-LIKE 3 promotes proliferation and migration in melanoma via MAPK activation.2015

    • Author(s)
      木庭幸子、内山彩、熊谷尚美、小川英作、奥山隆平
    • Organizer
      日本研究皮膚科学会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] DELTA-LIKE 3 promotes proliferation and migration in melanoma via MAPK activation.2015

    • Author(s)
      Yukiko Kiniwa, Aya Uchiyama, Naomi Kumagai, Eisaku Ogawa, Ryuhei Okuyama
    • Organizer
      Society for Melanoma Research
    • Place of Presentation
      Marriott Marquis(アメリカ,カリフォルニア州,サンフランシスコ)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Delta-like protein 3 promotes proliferation and migration of melanoma cells.2014

    • Author(s)
      Yukiko Kiniwa, Ryuhei Okuyama
    • Organizer
      European Society of Dermatological Research
    • Place of Presentation
      コペンハーゲン(デンマーク)
    • Year and Date
      2014-09-10 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 日本人におけるメラノーマの遺伝子異常2014

    • Author(s)
      木庭幸子、宇原久
    • Organizer
      日本皮膚科学会総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-05-30
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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