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3細胞間機能分子のヒト正常細胞の上皮バリアおよびがん細胞の悪性化抑制における役割

Research Project

Project/Area Number 18J15227
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

金野 匠  札幌医科大学, 医学部附属フロンティア医学研究所 細胞科学部門, 特別研究員(DC2)

Project Period (FY) 2018-04-25 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2019: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2018: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords上皮バリア機能 / LSR / Angubindin-1 / cytokinesis / YAP / ASPP2 / 3細胞間機能分子 / Tricellulin / ヒト子宮内膜癌細胞株 / JNK / cofilin / actin
Outline of Annual Research Achievements

本研究は、我々が確立したヒト正常上皮細胞およびLSRを高発現している癌細胞株や初代癌細胞株を用いて、ASPP2/LSR/AMOT/Merlin/YAP/PAR3蛋白複合体の正常および癌細胞における役割や発現調節メカニズムを多面的に解析することを目的としている。2019年度の実験計画として、ASPP2抗体を作製しASPP2機能阻害による癌の悪性化メカニズム解析とその抑制効果について検討することを主な内容としてきた。本研究での成果は以下の3点が挙げられる。
① LSR に特異的に結合し上皮および内皮バリアを低下させる LSR リガンド Angubindin-1に着目し、子宮内膜癌細胞株において Angubindin-1 が JNK/cofilin/actin cytoskeleton のダイナミクスを介して可逆的に上皮バリアを調節していることを報告した(Konno T et al., Tissue Barriers. 2020)。②子宮内膜癌細胞株において 3 細胞間タイト結合分子が細胞質分裂時の中央体や中心体に局在していることを見出し、LSR がヒト上皮細胞において、バリア機能だけでなく細胞質分裂時においても大きな役割を持っている可能性を報告した(Konno et al., J Histochem Cytochem. 2020)。③細胞死誘導を担い、タイト結合分子と共局在する Apoptosis-stimulating p53 protein 2 (ASPP2)に着目し、ASPP2 が子宮内膜癌において LSR や YAP を介して癌の悪性化の抑制に関与している可能性を報告した(Konno T et al., Histochem Cell Biol. 2020, in press)。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (20 results)

All 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Tricellular tight junction protein LSR/angulin-1 contributes to the epithelial barrier and malignancy in human pancreatic cancer cell line2020

    • Author(s)
      Kyuno T, Kyuno D, Kohno T, Konno T, Kikuchi S, Arimoto C, Yamaguchi H, Imamura M, Kimura Y, Kondoh M, Takemasa I, Kojima T
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 153 Issue: 1 Pages: 5-16

    • DOI

      10.1007/s00418-019-01821-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose-dependent FOXM1 promotes EMT via cellular metabolism and targeting snail in human pancreatic cancer2020

    • Author(s)
      Kyuno T, Kohno T, Konno T, Yamaguchi H, Kyuno D, Imamura M, Kimura Y, Kojima T and Takemasa I
    • Journal Title

      Pancreas

      Volume: 49 Issue: 2 Pages: 273-280

    • DOI

      10.1097/mpa.0000000000001485

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ASPP2 suppression promotes malignancy via LSR and YAP in human endometrial cancer.2020

    • Author(s)
      Konno T, Kohno T, Okada T, Shimada H, Satohisa S, Kikuchi S, Saito T, Kojima T.
    • Journal Title

      Histochem Cell Biol.

      Volume: 154(2) Issue: 2 Pages: 197-213

    • DOI

      10.1007/s00418-020-01876-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Tricellular Tight Junction Protein Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Cancer Cells2019

    • Author(s)
      Takayuki Kohno, Takumi Konno, Takashi Kojima
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 14 Pages: 3555-3555

    • DOI

      10.3390/ijms20143555

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Localization of Tricellular Tight Junction Molecule LSR at Midbody and Centrosome During Cytokinesis in Human Epithelial Cells2019

    • Author(s)
      Konno Takumi、Kohno Takayuki、Kikuchi Shin、Shimada Hiroshi、Satohisa Seiro、Takano Kenichi、Saito Tsuyoshi、Kojima Takashi
    • Journal Title

      Journal of Histochemistry & Cytochemistry

      Volume: 68 Issue: 1 Pages: 59-72

    • DOI

      10.1369/0022155419886263

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epithelial barrier dysfunction and cell migration induction via JNK/cofilin/actin by angubindin-12019

    • Author(s)
      Konno Takumi、Kohno Takayuki、Kikuchi Shin、Shimada Hiroshi、Satohisa Seiro、Saito Tsuyoshi、Kondoh Masuo、Kojima Takashi
    • Journal Title

      Tissue Barriers

      Volume: 8 Issue: 1 Pages: 1695475-1695475

    • DOI

      10.1080/21688370.2019.1695475

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of airway progenitor cells via p63 and KLF11 by Rho-kinase inhibitor Y27632 in hTERT-human nasal epithelial cells.2019

    • Author(s)
      Kaneko Y, Konno T, Kohno T, Kakuki T, Miyata R, Ohkuni T, Kakiuchi A, Yajima R, Ohwada K, Kurose M, Himi T, Takano K, Kojima T.
    • Journal Title

      Am. J. Transl. Res.

      Volume: 11(2) Pages: 599-611

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rho-kinase and PKCα Inhibition Induces Primary Cilia Elongation and Alters the Behavior of Undifferentiated and Differentiated Temperature-sensitive Mouse Cochlear Cells.2019

    • Author(s)
      Kakiuchi A, Kohno T, Kakuki T, Kaneko Y, Konno T, Hosaka Y, Hata T, Kikuchi S, Ninomiya T, Himi T, Takano K, Kojima T.
    • Journal Title

      J Histochem Cytochem.

      Volume: in press Issue: 7 Pages: 523-535

    • DOI

      10.1369/0022155419841013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guanylate binding protein-1-mediated epithelial barrier via tight junctions.2019

    • Author(s)
      Konno T, Kohno T, Takano K, Miyata R, Miyakawa M, Tanaka H, Kojima T.
    • Journal Title

      Epithelial Cells: Structure, Functions and Clinical Aspects. Nova Science Publishers.

      Volume: in press

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Guanylate binding protein-1-mediated epithelial barrier in human salivary gland duct epithelium2018

    • Author(s)
      Konno Takumi、Takano Kenichi、Kaneko Yakuto、Kakuki Takuya、Nomura Kazuaki、Yajima Ryoto、Kakiuchi Akito、Kohno Takayuki、Himi Tetsuo、Kojima Takashi
    • Journal Title

      Experimental Cell Research

      Volume: 371 Issue: 1 Pages: 31-41

    • DOI

      10.1016/j.yexcr.2018.07.033

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of fibrogenesis in submandibular glands in patients with IgG4-RD2018

    • Author(s)
      Yajima Ryoto、Takano Kenichi、Konno Takumi、Kohno Takayuki、Kaneko Yakuto、Kakuki Takuya、Nomura Kazuaki、Kakiuchi Akito、Himi Tetsuo、Kojima Takashi
    • Journal Title

      Journal of Molecular Histology

      Volume: 49 Issue: 6 Pages: 577-587

    • DOI

      10.1007/s10735-018-9796-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Loss of ASPP2 promotes cell invasion and migration via LSR and YAP in human endometrial cancer.2019

    • Author(s)
      Konno T, Kohno T, Shimada H, Satohisa S, Kikuchi S, Saito T, Kojima T.
    • Organizer
      第71回日本細胞生物学会 神戸 ポスター発表
    • Related Report
      2019 Annual Research Report
  • [Presentation] Loss of ASPP2 promotes cell invasion and migration via LSR and YAP in human endometrial cancer.2019

    • Author(s)
      Konno T, Kohno T, Shimada H, Satohisa S, Kikuchi S, Saito T, Kojima T.
    • Organizer
      第38回札幌国際がんシンポジウム 札幌 ポスター発表
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Loss of ASPP2 promotes cell invasion and migration via LSR and YAP in human endometrial cancer.2019

    • Author(s)
      Konno T, Kohno T, Shimada H, Satohisa S, Kikuchi S, Saito T, Kojima T.
    • Organizer
      第51回日本臨床分子形態学会総会 久留米 口演
    • Related Report
      2019 Annual Research Report
  • [Presentation] Loss of ASPP2 promotes cell invasion and migration via LSR and YAP in human endometrial cancer.2019

    • Author(s)
      Konno T, Kohno T, Shimada H, Satohisa S, Kikuchi S, Saito T, Kojima T.
    • Organizer
      ASCB 2019, Washington D.C., Poster presentation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Guanylate binding protein-1-meidated epithelial barrier in human salivary gland duct epithelium.2018

    • Author(s)
      Konno T, Takano K, Kaneko Y, Kakuki T, Nomura K, Yajima R, Kakiuchi A, Kohno T, Himi T, Kojima T.
    • Organizer
      第70回日本細胞生物学会 東京 ポスター発表
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3細胞間タイト結合分子LSRの発現低下によるがん細胞の悪性化の機序2018

    • Author(s)
      金野匠、幸野貴之、菊池真、嶋田浩志、郷久晴朗、齋藤豪、小島隆
    • Organizer
      第107回日本病理学会総会 札幌 口演
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト唾液腺管の上皮バリアはGBP-1を介して調節されている2018

    • Author(s)
      金野匠、高野賢一、金子躍人、角木拓也、野村一顕、矢島諒人、垣内晃人、幸野貴之、 氷見徹夫、小島隆
    • Organizer
      第51回北海道病理談話会 札幌 口演
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3細胞間タイト結合分子LSRリガンドAngubindin-1によるJNK/cofilin/actinを介した上皮バリア調節機構2018

    • Author(s)
      金野匠、幸野貴之、菊池真、嶋田浩志、郷久晴朗、齋藤豪、近藤昌夫、小島隆
    • Organizer
      第13回臨床ストレス応答学会 小樽 口演&ポスター発表
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3細胞間タイト結合分子Angulin-1/LSRリガンドAngubindin-1による上皮バリア調節機構2018

    • Author(s)
      金野匠、幸野貴之、菊池真、嶋田浩志、郷久晴朗、齋藤豪、近藤昌夫、小島隆
    • Organizer
      第41回日本分子生物学会 横浜 ポスター発表
    • Related Report
      2018 Annual Research Report

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Published: 2018-05-01   Modified: 2024-03-26  

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