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Identification of ALK-related ovarian cancer

Research Project

Project/Area Number 18K15092
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKitasato University

Principal Investigator

Inoue Hisako  北里大学, 医学部, 講師 (20813504)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsALK / 卵巣がん / 神経内分泌 / 卵巣漿液性癌 / 神経内分泌分化 / 卵巣癌 / HuC / 次世代シークエンサー / 神経内分泌マーカー / ovarian cancer
Outline of Final Research Achievements

ALK immunoreactivity was significantly higher in high-grade serous carcinoma(HGSC) and was significantly associated with several unfavorable clinicopathological factors. HGSC cell lines stably overexpressing ALK exhibited increased cell proliferation, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown (KD) cells. Expression of ELAVL3(HuC), as well as Sox2 and Sox3, were significantly increased in cells overexpressing ALK. Overexpression of Sox2 or Sox3 also enhanced both ALK and ELAVL3 promoter activities. Finally, ALK overexpression was due to increased expression of neuroendocrine markers including synaptophysin, CD56, and BCL2 in HGCS tissues. These findings suggest that overexpression of full-length ALK may influence the biological behavior of HGSC through cooperation with ELAVL3 and Sox factors, leading to establishment and maintenance of the aggressive phenotypic characteristics of HGSC.

Academic Significance and Societal Importance of the Research Achievements

①卵巣癌を「ALK遺伝子関連情報伝達異常」という観点からその生物学的特性、特にEMT/癌幹細胞化機構との関連性を分子病理学的に解析し、ALK関連卵巣癌という新たなカテゴリーを提唱する。②卵巣癌のALK発現と臨床病理学的因子との関連性から新たな予後予測システムを構築する。③ALK阻害剤などの分子標的薬や小化学化合物によるALK陽性卵巣癌の新規治療法開発の基盤を築く。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2021 2020 2019

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

  • [Journal Article] Anaplastic Lymphoma Kinase Overexpression Is Associated with Aggressive Phenotypic Characteristics of Ovarian High-Grade Serous Carcinoma2021

    • Author(s)
      Matsumoto T, Oda Y, Hasegawa Y, Hashimura M, Oguri Y, Inoue H, Yokoi A, Tochimoto M, Nakagawa M, Jiang Z, Saegusa M.
    • Journal Title

      Am J Pathol

      Volume: 191 Issue: 10 Pages: 1837-1837

    • DOI

      10.1016/j.ajpath.2021.06.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 卵巣癌におけるALK陽性癌の同定とその生物学的特性の解明2020

    • Author(s)
      小田祐介、松本俊英、三枝 信
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 卵巣漿液癌では全長型ALK発現が予後不良因子になる2019

    • Author(s)
      小田祐介、井上久子
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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