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Elucidation of the mechanism of endometrial cancer transformation mediated by nuclear pore complex factor

Research Project

Project/Area Number 19K07398
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionKanazawa University

Principal Investigator

Kobayashi Akiko  金沢大学, 新学術創成研究機構, 特任助教 (00345662)

Project Period (FY) 2019-04-01 – 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords核膜孔複合体 / ヌクレオポリン / 子宮内膜がん / 核膜孔複合体因子
Outline of Research at the Start

子宮内膜がんは悪性度の違いで二つのタイプに分かれ、女性ホルモン受容体の発現が低いタイプ2は悪性度が高く予後が悪い。しかし悪性化メカニズムは不明であり、悪性化した子宮内膜がんの病態制御に向けたターゲット因子の探索は重要な課題である。研究代表者は腫瘍の形成と進行への関与が近年注目されている核膜孔複合体(NPC)因子の一つと、タイプ2子宮内膜がん患者の生存率・女性ホルモン受容体の発現に相関を見出した。そこで本研究はNPC因子が関わる子宮内膜がん悪性化メカニズムを解明することを目的とし、NPC因子を含む悪性化シグナル経路とターゲット分子を同定、マウスを用いて悪性化メカニズムを検証する。

Outline of Final Research Achievements

The nuclear pore complex existing in the nuclear membrane is a huge complex composed of about 30 kinds of proteins called nucleoporins and is responsible for the transport of molecules between the nucleus and the cytoplasm. RAE1 is one of the nucleoporins and controls the nuclear export of mRNA. It was reported that RAE1 was highly expressed in various cancers and involved in the malignant transformation of cancers. We found that there is a correlation between the malignant transformation of cancer and the expression level of RAE1 in endometrial cancer. It is suggested that RAE1 switches partner molecules and controls exporting mRNA depend on malignancy.

Academic Significance and Societal Importance of the Research Achievements

研究代表者は、子宮内膜がんにおいて核膜孔複合体因子RAE1の発現がグレード依存的に上昇していること、がんの悪性化に伴いRAE1が相互作用分子を変えていることを見出した。これらのことから、RAE1が将来的に子宮内膜がんの悪性化のマーカーとなりうること、RAE1の発現制御によりがんの悪性化を防ぐ可能性が示された。

Report

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

    (36 results)

All 2022 2021 2020 2019

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 14 results) Presentation (22 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Discovery of a Novel Aminocyclopropenone Compound That Inhibits BRD4-Driven Nucleoporin NUP210 Expression and Attenuates Colorectal Cancer Growth2022

    • Author(s)
      Kondo Hiroya、Mishiro Kenji、Iwashima Yuki、Qiu Yujia、Kobayashi Akiko、Lim Keesiang、Domoto Takahiro、Minamoto Toshinari、Ogawa Kazuma、Kunishima Munetaka、Hazawa Masaharu、Wong Richard W.
    • Journal Title

      Cells

      Volume: 11 Issue: 3 Pages: 317-317

    • DOI

      10.3390/cells11030317

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NSP9 of SARS-CoV-2 attenuates nuclear transport by hampering nucleoporin 62 dynamics and functions in host cells2022

    • Author(s)
      Makiyama Kei、Hazawa Masaharu、Kobayashi Akiko、Lim Keesiang、Voon Dominic C.、Wong Richard W.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 586 Pages: 137-142

    • DOI

      10.1016/j.bbrc.2021.11.046

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Millisecond dynamic of SARS‐CoV‐2 spike and its interaction with ACE2 receptor and small extracellular vesicles2021

    • Author(s)
      Lim Keesiang、Nishide Goro、Yoshida Takeshi、Watanabe‐Nakayama Takahiro、Kobayashi Akiko、Hazawa Masaharu、Hanayama Rikinari、Ando Toshio、Wong Richard W.
    • Journal Title

      Journal of Extracellular Vesicles

      Volume: 10 Issue: 14

    • DOI

      10.1002/jev2.12170

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthetic zwitterions as efficient non-permeable cryoprotectants2021

    • Author(s)
      Kato Yui、Uto Takuya、Tanaka Daisuke、Ishibashi Kojiro、Kobayashi Akiko、Hazawa Masaharu、Wong Richard W.、Ninomiya Kazuaki、Takahashi Kenji、Hirata Eishu、Kuroda Kosuke
    • Journal Title

      Communications Chemistry

      Volume: 4 Issue: 1 Pages: 151-151

    • DOI

      10.1038/s42004-021-00588-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A light-switching pyrene probe to detect phase-separated biomolecules2021

    • Author(s)
      Hazawa Masaharu、Amemori Shogo、Nishiyama Yoshio、Iga Yoshihiro、Iwashima Yuki、Kobayashi Akiko、Nagatani Hirohisa、Mizuno Motohiro、Takahashi Kenji、Wong Richard W.
    • Journal Title

      iScience

      Volume: 24 Issue: 8 Pages: 102865-102865

    • DOI

      10.1016/j.isci.2021.102865

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Label-free tomographic imaging of nanodiamonds in living cells2021

    • Author(s)
      Ikliptikawati Dini Kurnia、Hazawa Masaharu、So Frederick T.-K.、Terada Daiki、Kobayashi Akiko、Segawa Takuya F.、Shirakawa Masahiro、Wong Richard W.
    • Journal Title

      Diamond and Related Materials

      Volume: 118 Pages: 108517-108517

    • DOI

      10.1016/j.diamond.2021.108517

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-Speed Atomic Force Microscopy Reveals Spatiotemporal Dynamics of Histone Protein H2A Involution by DNA Inchworming2021

    • Author(s)
      Nishide Goro、Lim Keesiang、Mohamed Mahmoud Shaaban、Kobayashi Akiko、Hazawa Masaharu、Watanabe-Nakayama Takahiro、Kodera Noriyuki、Ando Toshio、Wong Richard W.
    • Journal Title

      The Journal of Physical Chemistry Letters

      Volume: 12 Issue: 15 Pages: 3837-3846

    • DOI

      10.1021/acs.jpclett.1c00697

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex2021

    • Author(s)
      Kato Koki、Ikliptikawati Dini Kurnia、Kobayashi Akiko、Kondo Hiroya、Lim Keesiang、Hazawa Masaharu、Wong Richard W.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 536 Pages: 59-66

    • DOI

      10.1016/j.bbrc.2020.11.115

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-Speed AFM Reveals Molecular Dynamics of Human Influenza A Hemagglutinin and Its Interaction with Exosomes2020

    • Author(s)
      Lim Keesiang、Kodera Noriyuki、Wang Hanbo、Mohamed Mahmoud Shaaban、Hazawa Masaharu、Kobayashi Akiko、Yoshida Takeshi、Hanayama Rikinari、Yano Seiji、Ando Toshio、Wong Richard W.
    • Journal Title

      Nano Letters

      Volume: 20 Issue: 9 Pages: 6320-6328

    • DOI

      10.1021/acs.nanolett.0c01755

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spatiotemporally tracking of nano-biofilaments inside the nuclear pore complex core2020

    • Author(s)
      Mohamed Mahmoud Shaaban、Hazawa Masaharu、Kobayashi Akiko、Guillaud Laurent、Watanabe-Nakayama Takahiro、Nakayama Mizuho、Wang Hanbo、Kodera Noriyuki、Oshima Masanobu、Ando Toshio、Wong Richard W.
    • Journal Title

      Biomaterials

      Volume: 256 Pages: 120198-120198

    • DOI

      10.1016/j.biomaterials.2020.120198

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nucleoporin TPR (translocated promoter region, nulear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma.2020

    • Author(s)
      Dewi FRP, Jiapear S, Kobayashi A, Hazawa M, Ikliptikawati DK, Hartono, Sabit H, Nakada M, Wong RW
    • Journal Title

      Autophagy

      Volume: 24 Issue: 4 Pages: 1-12

    • DOI

      10.1080/15548627.2020.1741318

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disease-specific alteration of karyopherin-α subtype establishes feed-forward oncogenic signaling in head and neck squamous cell carcinoma2019

    • Author(s)
      Hazawa Masaharu、Sakai Kie、Kobayashi Akiko、Yoshino Hironori、Iga Yoshihiro、Iwashima Yuki、Lim Kee Sing、Chih-Cheng Voon Dominic、Jiang Yan-Yi、Horike Shin-ichi、Lin De-Chen、Wong Richard W.
    • Journal Title

      Oncogene

      Volume: 39 Issue: 10 Pages: 2212-2223

    • DOI

      10.1038/s41388-019-1137-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct Visualization of Avian Influenza H5N1 Hemagglutinin Precursor and its Conformational Change by High-Speed Atomic Force Microscopy2019

    • Author(s)
      Lim SK, Mohamed MS, Wang H, Hartono, Hazawa M, Kobayashi A, Voon DC, Kodera N, Ando T and Wong RW
    • Journal Title

      BBA - General Subjects

      Volume: 印刷中 Issue: 2 Pages: 129313-129313

    • DOI

      10.1016/j.bbagen.2019.02.015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nucleoporin Nup58 Localizes to centrosomes and mid-bodies during mitosis.2019

    • Author(s)
      Hartono, Hazawa M, Lim KS, Dewi FRP, Kobayashi A, Wong RW
    • Journal Title

      Cell Division

      Volume: 14 Issue: 1

    • DOI

      10.1186/s13008-019-0050-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The epigenetic role of nucleoporin RAE1 in human breast cancer2021

    • Author(s)
      Dini Kurnia Ikliptikawati, Akiko Kobayashi, Masaharu Hazawa, Richard W.Wong
    • Organizer
      The 39th Sapporo International Cancer Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核内相分離の制御を可能とする新規アミノシクロプロペノン化合物の発見2021

    • Author(s)
      近藤 寛弥、三代憲司、岩嶋友紀、Qiu Yujia、稲葉有香、小林亜紀子、Keesiang Lim、源利成、小川数馬、國嶋崇隆、羽澤勝治、Richard Wong
    • Organizer
      第39回染色体ワークショップ・第20回核ダイナミクス研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒストンH2A-DNAダイナミクスの実時空間イメージング2021

    • Author(s)
      西出梧朗、Keesiang Lim、小林亜紀子、羽澤勝治、稲葉有香、中山隆宏、古寺哲幸、安藤敏夫、Richard Wong
    • Organizer
      第39回染色体ワークショップ・第20回核ダイナミクス研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 核膜孔複合体による転写制御機構2021

    • Author(s)
      岩嶋友紀、羽澤勝治、Qiu Yujia、Dini Kurnia Ikliptikawati1、西 出 梧朗、小林 亜紀子、Lim Kee Siang、Richard Wong
    • Organizer
      第39回染色体ワークショップ・第20回核ダイナミクス研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] SARS-CoV-2由来ORF6は核膜孔複合体RAE1とNUP98の局在変化を引き起こす2021

    • Author(s)
      加藤弘毅、小林亜紀子、羽澤勝治、Richard W Wong
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Optical Diffraction Tomography as Label-Free High-Resolution 3-D Imaging of Nanodiamonds in Cancer Cell2021

    • Author(s)
      Dini Ikliptikawati, Masaharu Hazawa, Frederick So, Daiki Terada, Akiko Kobayahi, Takuya Segawa, Masahiro Shirakawa, Richard Wong
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 上衣腫における核膜孔複合体タンパク質Tprの役割2021

    • Author(s)
      小林亜紀子、Shabierjiang Jiapaer、Firli R.P. Dewi、羽澤勝治、Dini K. Ikliptikawati、Hartono、Hemragul Sabit、中田光俊、Richard Wong
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Molecular Dynamic of Coronavirus Spike Protein2021

    • Author(s)
      Keesiang Lim, Goro Nishide, Takeshi Yoshida, Takahiro Watanabe-Nakayama, Akiko Kobayashi, Masaharu Hazawa, Rikinari Hanayama, Toshio Ando, Richard W. Wong
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 液-液相分離の動態解析を可能とする機能性蛍光プローブ2021

    • Author(s)
      羽澤 勝治、雨森 翔悟、西山 嘉男、岩嶋 友紀、小林 亜紀子、永谷 広久、水野 元博、髙橋 憲司、ウォング リチャード
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高速AFMを用いたヒストンH2A-DNA実時空間イメージングによるヌクレオソーム凝縮プロセスとその環境の解明2021

    • Author(s)
      西出梧朗、Keesiang Lim、Mahmoud Shaaban Mohamed、小林亜紀子、羽澤勝治、中山隆宏、古寺哲幸、安藤敏夫、Richard Wong
    • Organizer
      第94回日本生化学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高速 AFM によるヒストン H2A トポグラフィーとその DNA コンパクション時の時空間ダイナミクスの解明2021

    • Author(s)
      西出梧朗、Keesiang Lim、小林亜紀子、羽澤勝治、中山隆宏、古寺哲幸、安藤敏夫、Richard Wong
    • Organizer
      第21回日本蛋白質科学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Investigation of real-time dynamic histone H2A-DNA interaction and H2A-DNA condensation/de-condensation using high-speed AFM2021

    • Author(s)
      西出梧朗、Keesiang LIM、小林亜紀子、羽澤勝治、中山隆宏、古寺哲幸、安藤敏夫、Richard WONG
    • Organizer
      第59回日本生物物理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規アミノシクロプロぺノン化合物はBRD4依存的なNUP210の発現を阻害し、がん細胞の増殖を抑制する2021

    • Author(s)
      近藤 寛弥、三代憲司、羽澤勝治、岩嶋友紀、小林亜紀子、小川数馬、Richard Wong
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高速 AFM を用いた DNA インチワーミングによるヒストン H2A ラッピング動態の実時空間イメージング2021

    • Author(s)
      西出梧朗、Keesiang Lim、小林亜紀子、羽澤勝治、中山隆宏、古寺哲幸、安藤敏夫、Richard Wong
    • Organizer
      第73回日本細胞生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規アミノシクロプロペノン化合物は BRD4 依存的 NUP210 の発現を阻害し、がん細胞の増殖を抑制する2021

    • Author(s)
      近藤 寛弥、三代憲司、羽澤勝治、岩嶋友紀、小林亜紀子、小川 数馬、Richard Wong
    • Organizer
      日本生化学会北陸支部第 39 回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] SARS-CoV-2由来ORF6は核膜孔複合体 RAE1とNUP98の局在変化を引き起こす2021

    • Author(s)
      加藤弘毅、小林亜紀子、羽澤勝治、Richard Wong
    • Organizer
      日本生化学会北陸支部第 39 回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高速 AFM を用いた DNA インチワーミングによるヒストン H2A ラッピング動態の実時空間イメージング2021

    • Author(s)
      西出梧朗、Keesiang Lim、Mahmoud Shaaban Mohamed、小林亜紀子、羽澤勝治、中山隆宏、古寺哲幸、安藤敏夫、Richard Wong
    • Organizer
      日本生化学会北陸支部第 39 回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 上衣腫における核膜孔複合体因子TPRの役割について2020

    • Author(s)
      小林 亜紀子、Dewi Firli、Jiapaer Shabierjiang、羽澤 勝治、Ikliptikawati Dini、Sabit Hemragul、中田 光俊、Richard Wong
    • Organizer
      第72回日本細胞生物学会大会(京都、オンライン)
    • Related Report
      2020 Research-status Report
  • [Presentation] NUP210ががん細胞の核サイズと増殖能力を調節する2020

    • Author(s)
      近藤 寛弥、三代 憲治、羽澤 勝治、小林 亜紀子、Richard Wong
    • Organizer
      第72回日本細胞生物学会大会(京都、オンライン)
    • Related Report
      2020 Research-status Report
  • [Presentation] 高速原子間力顕微鏡によるヒストンH2A動態の実時空間イメージング2020

    • Author(s)
      西出 梧朗、Keesiang Lim、Mahmoud Shaaban Mohamed、羽澤 勝治、小林 亜紀子、Richard Wong
    • Organizer
      第72回日本細胞生物学会大会(京都、オンライン)
    • Related Report
      2020 Research-status Report
  • [Presentation] High-Speed AFM Reveals Molecular Dynamics of Human Influenza A Hemagglutinin and Its Interaction with Exosomes2020

    • Author(s)
      Keesiang Lim, Noriyuki Kodera, Hanbo Wang, Mahmoud Shaaban Mohamed, Masaharu Hazawa, Akiko Kobayashi, Takeshi Yoshida, Rikinari Hanayama, Seiji Yano, Toshio Ando, Richard Wong
    • Organizer
      NanoLSI Symposium (4th) (Kanazawa)
    • Related Report
      2020 Research-status Report
  • [Presentation] Elucidation of histone H2A topography and its nanomechanics with DNA compaction using high-speed atomic force microscopy2020

    • Author(s)
      西出梧朗, Keesiang Lim, Mahmoud Shaaban Mohamed, 小林亜紀子, 羽澤勝治, Hanbo Wang, 中山隆宏, 古寺哲幸, 安藤敏夫, Richard Wong
    • Organizer
      第43回日本分子生物学会年会(オンライン)
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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