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The analysis of gene expression changes in the early stages of breast cancer metastasis using a zebrafish xenograft model.

Research Project

Project/Area Number 19K06454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionChiba University

Principal Investigator

Mizoguchi Takamasa  千葉大学, 大学院薬学研究院, 助教 (10645419)

Co-Investigator(Kenkyū-buntansha) 高橋 広夫  金沢大学, 薬学系, 准教授 (30454367)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsMIB1 / CTNND1 / 乳がん / 細胞移動 / E-cadherin / Mib1 / Ctnnd1 / 悪性化 / 異種移植モデル / 異種移植 / ゼブラフィッシュ / がん増殖 / がん転移 / RNA-seq / RNAseq / 遺伝子発現プロファイル
Outline of Research at the Start

がんにより生存率が低下する主因は転移である。ゼブラフィッシュ胚へのヒトがん細胞の異種移植モデルは、既存のモデルと比較して、迅速かつ多検体を取り扱うことができ、がん転移のライブイメージングも可能である。この利点を生かし、本研究では血管侵入したがん細胞と移植部にとどまったままのがん細胞の遺伝子発現プロファイルを取得、比較することにより、がん転移の初期段階に発現変動する遺伝子ネットワークを同定する。

Outline of Final Research Achievements

Database-based analysis and biochemical and cell biological analysis using various breast cancer-derived cell lines revealed that breast cancer cell migration is enhanced by decreased E3 ubiquitin ligase Mindbomb1 (MIB1) expression. In breast cancer cells, MIB1 stabilizes cell-cell adhesion and inhibits cell migration by regulating the protein level of Catenin delta1 (CTNND1), an E-cadherin interacting protein.
Our results suggest the possibility that breast cancer metastasis can be predicted by measuring the expression level of MIB1 and the protein level of CTNND1 in breast cancer cells in patients. In addition, our results also suggest that breast cancer metastasis may be inhibited by enhancing the function of MIB1. Therefore, our results may lead to new breast cancer therapies, such as treatment of the primary tumor while inhibiting metastasis by combining existing breast cancer treatment strategies.

Academic Significance and Societal Importance of the Research Achievements

乳がん患者のがん細胞におけるMIB1の発現レベル、CTNND1のタンパク質量レベルを計測することにより乳がんの転移しやすさが予測できることが示唆された。また本研究成果からMIB1の機能を亢進することで乳がんの転移を抑制できる可能性も考えられる。よって本研究成果は既存の乳がん治療戦略と併用することで、転移を抑制しつつ原発巣の根治治療を進めるといった、新たな乳がん治療の創出にもつながると考えられる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (39 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (24 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Small-Molecule-Mediated Suppression of BMP Signaling by Selective Inhibition of BMP1-Dependent Chordin Cleavage2023

    • Author(s)
      Mizoguchi Takamasa、Mikami Shohei、Yatou Mari、Kondo Yui、Omaru Shuhei、Kuwabara Shuhei、Okura Wataru、Noda Syouta、Tenno Takeshi、Hiroaki Hidekazu、Itoh Motoyuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 5 Pages: 4313-4313

    • DOI

      10.3390/ijms24054313

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Artificial Notch Signaling Activation Method Using Immobilized Ligand Beads2022

    • Author(s)
      Mizoguchi Takamasa、Handa Hikaru、Omaru Shuhei、Itoh Motoyuki
    • Journal Title

      Methods Mol Biol.

      Volume: 2472 Pages: 57-66

    • DOI

      10.1007/978-1-0716-2201-8_6

    • ISBN
      9781071622001, 9781071622018
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The guppy (Poecilia reticulata) is a useful model for analyzing age-dependent changes in metabolism, motor function, and gene expression2022

    • Author(s)
      Imai Moeno、Mizoguchi Takamasa、Wang Meng、Li Yingyi、Hasegawa Yoshinori、Tonoki Ayako、Itoh Motoyuki
    • Journal Title

      Experimental Gerontology

      Volume: 160 Pages: 111708-111708

    • DOI

      10.1016/j.exger.2022.111708

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Dexamethasone-Induced Osteoporosis In Vivo Using Zebrafish Scales2021

    • Author(s)
      Chaichit Siripat、Sato Takuto、Yu Huiqing、Tanaka Yu-ki、Ogra Yasumitsu、Mizoguchi Takamasa、Itoh Motoyuki
    • Journal Title

      Pharmaceuticals

      Volume: 14 Issue: 6 Pages: 536-536

    • DOI

      10.3390/ph14060536

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Py 3-FITC: a new fluorescent probe for live cell imaging of collagen-rich tissues and ionocytes2021

    • Author(s)
      Zhaotong Wang, Takamasa Mizoguchi, Takahito Kuribara, Masaya Nakajima, Mayuu Iwata, Yuka Sakamoto, Hiroyuki Nakamura, Toshihiko Murayama, Tetsuhiro Nemoto, Motoyuki Itoh
    • Journal Title

      Open Biology

      Volume: 11(2) Issue: 2 Pages: 200241-200241

    • DOI

      10.1098/rsob.200241

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient activation of the Notch-her15.1 axis plays an important role in the maturation of V2b interneurons2020

    • Author(s)
      Takamasa Mizoguchi 1, Michi Fukada 1, Miku Iihama 1, Xuehui Song 1, Shun Fukagawa 1, Shuhei Kuwabara 1, Shuhei Omaru 1, Shin-Ichi Higashijima 2 3, Motoyuki Itoh 4
    • Journal Title

      Development

      Volume: 147(16) Issue: 16

    • DOI

      10.1242/dev.191312

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] The formation of perinucleolar bodies is important for normal leaf development and requires the zinc‐finger DNA‐binding motif in Arabidopsis ASYMMETRIC LEAVES22020

    • Author(s)
      Luo Lilan、Ando Sayuri、Sakamoto Yuki、Suzuki Takanori、Takahashi Hiro、Ishibashi Nanako、Kojima Shoko、Kurihara Daisuke、Higashiyama Tetsuya、Yamamoto Kotaro T.、Matsunaga Sachihiro、Machida Chiyoko、Sasabe Michiko、Machida Yasunori
    • Journal Title

      The Plant Journal

      Volume: 101 Issue: 5 Pages: 1118-1134

    • DOI

      10.1111/tpj.14579

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive genome-wide identification of angiosperm upstream ORFs with peptide sequences conserved in various taxonomic ranges using a novel pipeline, ESUCA2020

    • Author(s)
      Takahashi Hiro、Hayashi Noriya、Hiragori Yuta、Sasaki Shun、Motomura Taichiro、Yamashita Yui、Naito Satoshi、Takahashi Anna、Fuse Kazuyuki、Satou Kenji、Endo Toshinori、Kojima Shoko、Onouchi Hitoshi
    • Journal Title

      BMC Genomics

      Volume: 21 Issue: 1 Pages: 260-260

    • DOI

      10.1186/s12864-020-6662-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Excess sterols disrupt plant cellular activity by inducing stress-responsive gene expression2020

    • Author(s)
      Shimada Takashi L、Yamaguchi Katsuki、Shigenobu Shuji、Takahashi Hiro、Murase Masataka、Fukuyoshi Shuichi、Hara-Nishimura Ikuko
    • Journal Title

      Journal of Plant Research

      Volume: in press Issue: 3 Pages: 383-392

    • DOI

      10.1007/s10265-020-01181-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Draft Genome Sequence of Aspergillus terreus High-Itaconic-Acid- Productivity Strain IFO63652020

    • Author(s)
      Takahashi H., Minami T., Okabe M., Park E.Y., Fujimoto T., Takahashi A., Murase M., Fukuyoshi S., Satou K., and Kanamasa S.
    • Journal Title

      Microbiol. Resour. Announc.

      Volume: - Issue: 16 Pages: 1-2

    • DOI

      10.1128/mra.00080-20

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SIMON: Simple methods for analyzing DNA methylation by targeted bisulfite next-generation sequencing2019

    • Author(s)
      Vial-Pradel Simon、Hasegawa Yoshinori、Nakagawa Ayami、Miyaki Shido、Machida Yasunori、Kojima Shoko、Machida Chiyoko、Takahashi Hiro
    • Journal Title

      Plant Biotechnology

      Volume: 36 Issue: 4 Pages: 213-222

    • DOI

      10.5511/plantbiotechnology.19.0822a

    • NAID

      130007776104

    • ISSN
      1342-4580, 1347-6114
    • Year and Date
      2019-12-25
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance2019

    • Author(s)
      Kenji Kita, Koji Fukuda, Hiro Takahashi, Azusa Tanimoto, Akihiro Nishiyama, Sachiko Arai, Shinji Takeuchi, Kaname Yamashita, Koshiro Ohtsubo, Sakiko Otani, Naohiro Yanagimura, Chiaki Suzuki, Hiroko Ikeda, Masaya Tamura, Isao Matsumoto, Seiji Yano
    • Journal Title

      Cancer Science

      Volume: 110(10) Issue: 10 Pages: 3215-3224

    • DOI

      10.1111/cas.14171

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Draft Genome Sequence of Aspergillus terreus High-Itaconic-Acid-Productivity Mutant TN-4842019

    • Author(s)
      Kanamasa Shin、Minami Tomoyuki、Okabe Mitsuyasu、Park Enoch Y.、Fujimoto Tsukasa、Takahashi Anna、Murase Masataka、Fukuyoshi Shuichi、Oda Akifumi、Satou Kenji、Takahashi Hiro
    • Journal Title

      Microbiology Resource Announcements

      Volume: 8 Issue: 49

    • DOI

      10.1128/mra.01170-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Draft Genome Sequence of Saccharomyces cerevisiae Strain Pf-1, Isolated from Prunus mume2019

    • Author(s)
      Kanamasa Shin、Yamaguchi Daiki、Machida Chiyoko、Fujimoto Tsukasa、Takahashi Anna、Murase Masataka、Fukuyoshi Shuichi、Oda Akifumi、Satou Kenji、Takahashi Hiro
    • Journal Title

      Microbiology Resource Announcements

      Volume: 8 Issue: 46

    • DOI

      10.1128/mra.01169-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] E3ユビキチンライゲースMIB1はCTNND1の安定化を介して乳がん細胞の移動を制御している2023

    • Author(s)
      加納 永梧、魯 靖雨 、溝口 貴正、伊藤 素行
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Aging affects vascular function and exacerbate cerebral infarction symptom in the zebrafish telencephalon.2022

    • Author(s)
      Mayu Okita, Yuina Minami, Misa Fukunaga, Ayumi Maki, Takamasa Mizoguchi, Motoyuki Itoh
    • Organizer
      第28回小型魚類研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ゼブラフィッシュ脳梗塞モデルを用いた高脂肪食肥満による脳機能低下と脳梗塞病態に与える影響の解析2022

    • Author(s)
      福永 美沙、南 唯菜、大北 真由、溝口 貴正、伊藤 素行
    • Organizer
      第66回薬学会関東支部会
    • Related Report
      2022 Annual Research Report
  • [Presentation] モデルゼブラフィッシュの病態解析による血管性認知症CADASILの発症機構の解明2022

    • Author(s)
      王林 思帆、古川 健吾、楊 鵬、溝口 貴正、伊藤 素行
    • Organizer
      第66回薬学会関東支部会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高脂肪食の過食による肥満が脳機能と脳梗塞病態に与える影響の解析2022

    • Author(s)
      福永 美沙、南 唯菜、大北 真由、溝口 貴正、伊藤 素行
    • Organizer
      第8回ゼブラフィッシュ・メダカ創薬研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ゼブラフィッシュ終脳を用いた脳梗塞後の回復過程における遺伝子発現の時系列解析2022

    • Author(s)
      牧 愛優美、福永 美沙、南 唯菜、大北 真由、溝口 貴正、伊藤 素行
    • Organizer
      第8回ゼブラフィッシュ・メダカ創薬研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] E3ユビキチンライゲースMIB1の発現は乳がん増殖に影響する2022

    • Author(s)
      加納 永梧、溝口 貴正、伊藤 素行
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] ゼブラフィッシュを用いた慢性ストレスが脳機能に与える影響の解析2021

    • Author(s)
      今井 晴菜、栗山 満里奈、溝口 貴正、伊藤 素行
    • Organizer
      第65回薬学会関東支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 高脂肪食過食によるゼブラフィッシュ耐糖能異常モデルの作製と病態誘導遺伝子探索2021

    • Author(s)
      石井謙介、梶原理希、小西尚子、殿城亜矢子、溝口貴正、伊藤素行
    • Organizer
      第65回薬学会関東支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Igf2bp3 is involved in age-related memory impairment and motor dysfunction2021

    • Author(s)
      Moeno Imai, Takamasa Mizoguchi, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      The 27th Japanese Medaka and Zebrafish Meeting
    • Related Report
      2021 Research-status Report
  • [Presentation] Chronic immobilization stress changes lipid metabolism and affects brain functions in adult zebrafish2021

    • Author(s)
      Haruna Imai, Marina Kuriyama, Takamasa Mizoguchi, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      The 27th Japanese Medaka and Zebrafish Meeting
    • Related Report
      2021 Research-status Report
  • [Presentation] Genetic background and aging affect glucose tolerance in adult zebrafish2021

    • Author(s)
      Kensuke Ishii, Riki Kajiwara, Naoko Konishi, Takamasa Mizoguchi, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      The 27th Japanese Medaka and Zebrafish Meeting
    • Related Report
      2021 Research-status Report
  • [Presentation] Mib1 is involved in the modulation of the Sept9 protein level and contributes to cytokinesis2021

    • Author(s)
      Takamasa Mizoguchi, Motoyuki Itoh
    • Organizer
      第44回分子生物学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Igf2bp3 Deficiency Causes Premature Aging Phenotypes2021

    • Author(s)
      Moeno Imai, Takamasa Mizoguchi, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      CELL BIO
    • Related Report
      2021 Research-status Report
  • [Presentation] 加齢や肥満がゼブラフィッシュ脳梗塞モデルの病態および回復過程に与える2021

    • Author(s)
      福永 美沙、牧 愛優美、大北 真由、南 唯菜、溝口 貴正、伊藤 素行
    • Organizer
      第7回ゼブラフィッシュ・メダカ創薬研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] Age-associated changes of systemic metabolism and gene expression in adult Guppy (Poecilia reticulata)2020

    • Author(s)
      Moeno Imai, Takamasa Mizoguchi, Meng Wang, Yingyi Li, Yoshinori Hasegawa, Ayako Tonoki, Motoyuki Itoh
    • Organizer
      The 26th Japanese Medaka and Zebrafish Meeting (JMZM)
    • Related Report
      2020 Research-status Report
  • [Presentation] The glioma transplanted zebrafish model is useful to investigate the resistance of glioma cells to Notch inhibitors2020

    • Author(s)
      馬 嘉帷、桑原 周平、溝口 貴正、伊藤 素行
    • Organizer
      第6回ゼブラフィッシュ・メダカ創薬研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] ゼブラフィッシュ脳梗塞モデルを用いた加齢が脳機能回復に与える影響の解析2020

    • Author(s)
      南唯菜、大北真由、溝口貴正、伊藤素行
    • Organizer
      第64回日本薬学会 関東支部大会
    • Related Report
      2020 Research-status Report
  • [Presentation] A new live staining probe,FITC-BPC3:for zebrafish fibrous tissues2019

    • Author(s)
      Zhaotong Wang, Takahito Kurihara. Seiya Nakajima , Takamasa Mizoguchi , Tetsuhiro Nemoto and Motoyuki Itoh.
    • Organizer
      第25回小型魚類研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] ゼブラフィッシュ成魚を用いた脳梗塞モデルの確立と脳機能回復過程の解析2019

    • Author(s)
      大北 真由、溝口 貴正、伊藤 素行
    • Organizer
      第5回創薬ゼブラフィッシュメダカ研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] A new live staining probe,FITC-BPC3:for zebrafish fibrous tissues2019

    • Author(s)
      Zhaotong Wang, Takahito Kurihara. Seiya Nakajima , Takamasa Mizoguchi , Tetsuhiro Nemoto and Motoyuki Itoh.
    • Organizer
      第5回創薬ゼブラフィッシュメダカ研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of bioinformatics methods and their applications: from plant to medical sciences2019

    • Author(s)
      Takahashi H., Machida C., Muto M., Kojima S., Itoh M., Onouchi H., and Sasaki H.
    • Organizer
      International Conference for Leading and Young Medical Scientists - IC-LYMS 2019 -
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 翻訳制御上流ORFのバイオインフォマティクスによる推定と実験的検証2019

    • Author(s)
      宮木至道、林憲哉、尾之内均、伊藤素行、高橋広夫
    • Organizer
      日本遺伝学会第91回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ゲノムのジャンク領域における機能領域予測とその実験的検証2019

    • Author(s)
      本村汰一朗、宮木至道、林憲哉、尾之内均、伊藤素行、高橋広夫
    • Organizer
      第48回東海ファジィ研究会
    • Related Report
      2019 Research-status Report
  • [Remarks] 千葉大学薬学部生化学研究室ホームページ

    • URL

      http://www.p.chiba-u.jp/lab/seika/index.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

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