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Molecular mechanisms of CLDN-ER axis regulating the breast and endometrial cancer progression

Research Project

Project/Area Number 19K16615
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionFukushima Medical University

Principal Investigator

Sugimoto Kotaro  福島県立医科大学, 医学部, 講師 (40791009)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん / 細胞間接着 / 核内受容体 / 乳癌 / 子宮体癌 / 婦人科癌 / 細胞接着 / 転写因子
Outline of Research at the Start

申請者は細胞間接着分子クローディンから核内受容体に至る新規シグナル伝達経路を発見した。またこの標的がエストロゲン受容体(ER)にも存在することを端緒とし、CLDN-ER連関による新たな腫瘍細胞の制御機構を着想した。本研究では分子生物学的アプローチと臨床病理検体の解析を組合せ、ER-CLDN連関に着目した次世代のがん個別化治療戦略を見据えた新知見を確立する。

Outline of Final Research Achievements

We discovered a novel signaling pathway from the tight junction protein claudin-6 and ending to nuclear receptors, which triggers the epithelial differentiation of stem cells. We subsequently showed that claudin-6 is a poor prognostic factor for uterine cancer. In addition, we found that the mechanism is due to the abnormal activation of a signaling pathway between claudin-6 and estrogen receptor-alpha, one of the nuclear receptors. On the other hand, in breast cancer, abnormal activation and its involvement in cancer progression of the signal from claudin-4 to another nuclear receptor, the liver X receptor, has also been suggested.

Academic Significance and Societal Importance of the Research Achievements

核内受容体は天然の脂質リガンドによって活性化されるが、リン酸化などの翻訳後修飾によっても制御されている。前者は比較的よく研究されていたが、後者はあまりよく解っていない。本研究では核内受容体の異常リン酸化が腫瘍の悪性形質制御に影響することを明らかにし、これが新規診断マーカーであると共に潜在的な治療標的である可能性が示唆された。本研究は新規創薬など個別化がん治療戦略の発展に寄与するものである。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (15 results)

All 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Bacterial Myocarditis in a Patient with Cancer2021

    • Author(s)
      Yamashita Rina, Tanaka Mizuko, Chiba Hideki, Sugimoto Kotaro
    • Journal Title

      JMA Journal

      Volume: 4 Issue: 2 Pages: 169-170

    • DOI

      10.31662/jmaj.2020-0082

    • NAID

      130008035749

    • ISSN
      2433-328X, 2433-3298
    • Year and Date
      2021-04-15
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The claudin?transcription factor signaling pathway2021

    • Author(s)
      Sugimoto Kotaro、Chiba Hideki
    • Journal Title

      Tissue Barriers

      Volume: 9 Issue: 3 Pages: 1-1

    • DOI

      10.1080/21688370.2021.1908109

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer2021

    • Author(s)
      Rahman Abidur、Kobayashi Makoto、Sugimoto Kotaro、Endo Yuta、Kojima Manabu、Furukawa Shigenori、Watanabe Takafumi、Soeda Shu、Hashimoto Yuko、Fujimori Keiya、Chiba Hideki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 7 Pages: 3774-3774

    • DOI

      10.3390/ijms22073774

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kruppel-like factor 1 is a core cardiomyogenic trigger in zebrafish2021

    • Author(s)
      Ogawa Masahito、Geng Fan-Suo、Humphreys David T.、Kristianto Esther、Sheng Delicia Z.、Hui Subhra P.、Zhang Yuxi、Sugimoto Kotaro、Nakayama Maki、Zheng Dawei、Hesselson Daniel、Hodson Mark P.、Bogdanovic Ozren、Kikuchi Kazu
    • Journal Title

      Science

      Volume: 372 Issue: 6538 Pages: 201-205

    • DOI

      10.1126/science.abe2762

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Aberrant Claudin-6?Adhesion Signaling Promotes Endometrial Cancer Progression via Estrogen Receptor α2021

    • Author(s)
      Kojima Manabu、Sugimoto Kotaro、Kobayashi Makoto、Ichikawa-Tomikawa Naoki、Kashiwagi Korehito、Watanabe Takafumi、Soeda Shu、Fujimori Keiya、Chiba Hideki
    • Journal Title

      Molecular Cancer Research

      Volume: 19 Issue: 7 Pages: 1208-1220

    • DOI

      10.1158/1541-7786.mcr-20-0835

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells2021

    • Author(s)
      Yamazaki Morio、Sugimoto Kotaro、Mabuchi Yo、Yamashita Rina、Ichikawa-Tomikawa Naoki、Kaneko Tetsuharu、Akazawa Chihiro、Hasegawa Hiroshi、Imura Tetsuya、Chiba Hideki
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 3 Pages: 278-278

    • DOI

      10.3390/biomedicines9030278

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The region‐selective regulation of endothelial claudin‐5 expression and signaling in brain health and disorders2021

    • Author(s)
      Chiba Hideki、Ichikawa‐Tomikawa Naoki、Imura Tetsuya、Sugimoto Kotaro
    • Journal Title

      Journal of Cellular Physiology

      Volume: in press Issue: 10 Pages: 7134-7143

    • DOI

      10.1002/jcp.30357

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serotonin/5-HT1A Signaling in the Neurovascular Unit Regulates Endothelial CLDN5 Expression2020

    • Author(s)
      Sugimoto Kotaro、Ichikawa-Tomikawa Naoki、Nishiura Keisuke、Kunii Yasuto、Sano Yasuteru、Shimizu Fumitaka、Kakita Akiyoshi、Kanda Takashi、Imura Tetsuya、Chiba Hideki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 1 Pages: 254-254

    • DOI

      10.3390/ijms22010254

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer2020

    • Author(s)
      Kojima Manabu、Sugimoto Kotaro、Tanaka Mizuko、Endo Yuta、Kato Hitomi、Honda Tsuyoshi、Furukawa Shigenori、Nishiyama Hiroshi、Watanabe Takafumi、Soeda Shu、Fujimori Keiya、Chiba Hideki
    • Journal Title

      Cancers

      Volume: 12 Issue: 10 Pages: 2748-2748

    • DOI

      10.3390/cancers12102748

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of the Lactococcus Lactis 11/19-B1 Strain on Atopic Dermatitis in a Clinical Test and Mouse Model2020

    • Author(s)
      Suzuki Takato、Nishiyama Kyoko、Kawata Koji、Sugimoto Kotaro、Isome Masato、Suzuki Shigeo、Nozawa Ruriko、Ichikawa Yoko、Watanabe Yoshihisa、Suzutani Tatsuo
    • Journal Title

      Nutrients

      Volume: 12 Issue: 3 Pages: 763-763

    • DOI

      10.3390/nu12030763

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell adhesion signals regulate the nuclear receptor activity2019

    • Author(s)
      Sugimoto Kotaro、Ichikawa-Tomikawa Naoki、Kashiwagi Korehito、Endo Chihiro、Tanaka Satoshi、Sawada Norimasa、Watabe Tetsuya、Higashi Tomohito、Chiba Hideki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 49 Pages: 24600-24609

    • DOI

      10.1073/pnas.1913346116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] クローディン-6による子宮体癌の悪性形質増強機構2020

    • Author(s)
      杉本 幸太郎
    • Organizer
      日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 組織再生の最前線 - ゼブラフィッシュ2019

    • Author(s)
      杉本 幸太郎
    • Organizer
      日本病理学会カンファレンス
    • Related Report
      2019 Research-status Report
  • [Presentation] タイト結合分子クローディンに対するモノクローナル抗体の樹立とその応用2019

    • Author(s)
      杉本 幸太郎
    • Organizer
      日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 女性ホルモン依存性がんの悪性度及び予後の判定のためのバイオマーカー2020

    • Inventor(s)
      杉本 幸太郎、千葉 英樹
    • Industrial Property Rights Holder
      杉本 幸太郎、千葉 英樹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2023-12-25  

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