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Mechanisms underlying Src-mediated exosome upregulation in cancer cells

Research Project

Project/Area Number 20H03456
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Oneyama Chitose  愛知県がんセンター(研究所), 腫瘍制御学分野, 分野長 (90373208)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2022: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
KeywordsSrc / がん / エクソソーム / がん進展 / Srcシグナル
Outline of Research at the Start

Srcシグナルの支配するエクソソーム分泌が、がん進展に果たす役割とそのメカニズムを明らかにしたい。これまで、エクソソーム分泌が細胞のがん形質発現と不可分な現象であり、そこにSrcシグナルの制御破綻が深く関与していることを見出してきた。従って、その詳細な分子メカニズムを解明することは、細胞のがん化およびその悪性化の機構に新たな洞察をもたらすと期待できる。さらに本研究では、がんエクソソームにより近隣あるいは遠隔細胞へと、いわば“細胞外Srcシグナル”が伝播される可能性を想定し、その動態とがん病態との関わりを解明していく。

Outline of Final Research Achievements

The proto-oncogene product Src is upregulated in many cancer tissues, and it has been shown that Src-related signaling pathways are involved in the expression of various cancer traits such as cell growth and invasion. In this study, we analyzed the mechanism of cancer-specific exosome upregulation by Src to elucidate the action of Src signaling in the establishment of the cancer microenvironment via exosomes.

Academic Significance and Societal Importance of the Research Achievements

様々ながんでエクソソーム分泌が亢進し、内包miRNAや蛋白質が変化すると報告されている。その結果、エクソソームを利用したがん診断への応用研究が加速している。しかし、がん特異的なエクソソーム分泌の分子メカニズムには不明な点が多い。本研究においてその詳細な分子基盤を解明することによって、がん進展メカニズムに対する理解を深め、新たながん制御戦略へつなげることができると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (45 results)

All 2023 2022 2021 2020 Other

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (29 results) (of which Invited: 11 results) Remarks (2 results)

  • [Journal Article] Metabolomics of small extracellular vesicles derived from isocitrate dehydrogenase 1-mutant HCT116 cells collected by semi-automated size exclusion chromatography2023

    • Author(s)
      Hayasaka Ryosuke、Tabata Sho、Hasebe Masako、Ikeda Satsuki、Hikita Tomoya、Oneyama Chitose、Yoshitake Jun、Onoshima Daisuke、Takahashi Kumiko、Shibata Takahiro、Uchida Koji、Baba Yoshinobu、Soga Tomoyoshi、Tomita Masaru、Hirayama Akiyoshi
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 9 Pages: 1049402-1049402

    • DOI

      10.3389/fmolb.2022.1049402

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SNAP23-Mediated Perturbation of Cholesterol-Enriched Membrane Microdomain Promotes Extracellular Vesicle Production in Src-Activated Cancer Cells2022

    • Author(s)
      Mitani F, Hayasaka R, Hirayama A, Oneyama C
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 45 Issue: 10 Pages: 1572-1580

    • DOI

      10.1248/bpb.b22-00560

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2022-10-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification and imaging of exosomes via luciferase-fused exosome marker proteins: ExoLuc system.2022

    • Author(s)
      Hikita T, Oneyama C
    • Journal Title

      Methods Mol Biol

      Volume: 2524 Pages: 281-290

    • DOI

      10.1007/978-1-0716-2453-1_21

    • ISBN
      9781071624524, 9781071624531
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asteltoxin inhibits extracellular vesicle production through AMPK/mTOR-mediated activation of lysosome function.2022

    • Author(s)
      Mitani F, Lin J, Sakamoto T, Uehara R, Hikita T, Yoshida T, Setiawan A, Arai M, Oneyama C.
    • Journal Title

      Sci Rep

      Volume: 12 Issue: 1 Pages: 6674-6674

    • DOI

      10.1038/s41598-022-10692-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MEK/ERK‐mediated oncogenic signals promote secretion of extracellular vesicles by controlling lysosome function2022

    • Author(s)
      Hikita Tomoya、Uehara Ryo、Itoh Reina E.、Mitani Fumie、Miyata Mamiko、Yoshida Takuya、Yamaguchi Rui、Oneyama Chitose
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 4 Pages: 1264-1276

    • DOI

      10.1111/cas.15288

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their diseaseassociated regulation.2022

    • Author(s)
      Morioka S, Nakanishi H, Yamamoto T, Hasegawa J, Tokuda E, Hikita T, Sakihara T, Kugii Y, Oneyama C, Yamazaki M, Suzuki A, Sasaki J, Sasaki T.
    • Journal Title

      Nature Communications

      Volume: 13(1) Issue: 1 Pages: 83-83

    • DOI

      10.1038/s41467-021-27648-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction.2021

    • Author(s)
      Ito Reina E, Oneyama Chitose, Aoki Kazuhiro
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 4 Pages: e0249388-e0249388

    • DOI

      10.1371/journal.pone.0249388

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes secreted from cancer-associated fibroblasts elicit anti-pyrimidine drug resistance through modulation of its transporter in malignant lymphoma.2021

    • Author(s)
      Kunou S, Shimada K, Takai M, Sakamoto A, Aoki T, Hikita T, Kagaya Y, Iwamoto E, Sanada M, Shimada S, Hayakawa F, Oneyama C, Kiyoi H.
    • Journal Title

      Oncogene

      Volume: 40 Issue: 23 Pages: 3989-4003

    • DOI

      10.1038/s41388-021-01829-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] がんシグナルによる細胞外小胞の分泌亢進メカニズム2021

    • Author(s)
      小根山千歳
    • Journal Title

      実験医学

      Volume: 39 Pages: 3141-3147

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells2021

    • Author(s)
      Tamako Nishimura*, Takuya Oyama*, Hooi Ting Hu*, Toshifumi Fujioka* et al.(*:equally contributed)
    • Journal Title

      Developmental Cell

      Volume: 56 Issue: 6 Pages: 842

    • DOI

      10.1016/j.devcel.2021.02.029

    • NAID

      120007172296

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] c-Src promotes tumor progression through downregulation of microRNA-129-1-3p2020

    • Author(s)
      Daisuke Okuzaki, Tomoe Yamauchi, Fumie Mitani, Mamiko Miyata, Risayo Watanabe, Chitose Oneyama
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 2 Pages: 418-428

    • DOI

      10.1111/cas.14269

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells.2020

    • Author(s)
      Watanabe R, Miyata M, Oneyama C.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 531 Issue: 4 Pages: 636-642

    • DOI

      10.1016/j.bbrc.2020.08.012

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter2020

    • Author(s)
      Tomoya Hikita, Mamiko Miyata, Risayo Watanabe, Chitose Oneyama
    • Journal Title

      Scientific Reports

      Volume: 10(1) Issue: 1 Pages: 16616-16616

    • DOI

      10.1038/s41598-020-73580-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] チロシンキナーゼ:分子標的薬を極める2020

    • Author(s)
      小根山千歳
    • Journal Title

      産科と婦人科

      Volume: 87 Pages: 1150-1155

    • Related Report
      2020 Annual Research Report
  • [Presentation] がんシグナルが制御する細胞のかたちと細胞外小胞2023

    • Author(s)
      小根山千歳
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がんシグナルによるエクソソーム産生亢進メカニズム2022

    • Author(s)
      小根山千歳
    • Organizer
      名古屋大学創薬科学研究科セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がん原遺伝子Srcの再考-新規分子標的を求めて2022

    • Author(s)
      小根山千歳
    • Organizer
      千里ライフサイエンス新適塾第52回「難病への挑戦」
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Ferキナーゼを標的とした革新的がん治療薬の開発2022

    • Author(s)
      小根山千歳
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Ferキナーゼを標的とした新規がん治療薬の創出を目指して2022

    • Author(s)
      小根山千歳
    • Organizer
      第26回日本がん分子標的治療学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] AsteltoxinはAMPK-mTORを介したリソソーム機能亢進によってエクソソーム産生を阻害する2022

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MEK/ERKシグナルの活性化はリソソーム形成の抑制を介してエクソソーム分泌を促進する2022

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MEK/ERK経路活性化によるがんエクソソーム分泌亢進メカニズムの解析2022

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第4回CIBoGリトリート
    • Related Report
      2022 Annual Research Report
  • [Presentation] SNAP23を介したSrc依存的エクソソーム産生亢進メカニズム2022

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第9回日本細胞外小胞学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MEK/ERK経路を介したがんEV分泌亢進メカニズムの解析2022

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第9回日本細胞外小胞学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] RAB27A発現を制御する新規EV分泌阻害剤の同定2022

    • Author(s)
      上原了、小根山千歳
    • Organizer
      第9回日本細胞外小胞学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] がん細胞由来細胞外小胞を標的とした新規阻害剤の探索2022

    • Author(s)
      上原了、小根山千歳
    • Organizer
      先端モデル動物支援プラットフォーム 若手支援技術講習会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Asteltoxin suppresses extracellular vesicle secretion through AMPK/mTOR-mediated activation of lysosome function2022

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第3回CIBoGリトリート/第14回NAGOYAグローバルリトリート
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mechanisms underlying the oncogenic signal-mediated exosome upregulation.2021

    • Author(s)
      小根山千歳
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 発光を利用したがんエクソソーム産生亢進機構の解明2021

    • Author(s)
      小根山千歳
    • Organizer
      第31回基礎及び最新の分析化学講習会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がんシグナルによるエクソソーム分泌亢進メカニズム2021

    • Author(s)
      小根山千歳
    • Organizer
      第8回日本細胞外小胞学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がん細胞由来エクソソームのin vivoイメージング2021

    • Author(s)
      小根山千歳
    • Organizer
      第25回日本がん分子標的治療学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter2021

    • Author(s)
      Chitose Oneyama
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] エクソソーム産生機構解明に向けた分泌制御因子の解析2021

    • Author(s)
      中山真穂、小野島大介、湯川博、小根山千歳、馬場嘉信
    • Organizer
      日本化学会第101回春季大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 海洋薬用資源からのがんエクソソーム分泌阻害物質の探索2021

    • Author(s)
      林建宇、三谷文美絵、小根山千歳、荒井雅吉
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がんにおけるエクソソームの分泌亢進メカニズム2020

    • Author(s)
      小根山千歳
    • Organizer
      第72回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] がん細胞由来エクソソームのin vivoイメージング2020

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第72回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Src依存的エクソソーム分泌亢進におけるSNAREタンパク質の機能2020

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第72回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] In vivo imaging of long-term accumulated cancer-derived exosomes by CD63-fused BRET reporter2020

    • Author(s)
      Tomoya Hikita, Chitose Oneyama
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The role of SNARE-protein on the Src-mediated upregulation of exosome secretion2020

    • Author(s)
      Fumie Mitani, Chitose Oneyama
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞由来エクソソームのin vivoイメージング解析2020

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第7回日本細胞外小胞学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Src依存的エクソソーム分泌亢進におけるSNAREタンパク質の役割2020

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第7回日本細胞外小胞学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞のエクソソームの分泌亢進機構とその意義2020

    • Author(s)
      小根山千歳
    • Organizer
      第93回生化学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanisms governing exosome biogenesis in cancer cells2020

    • Author(s)
      小根山千歳
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 愛知県がんセンター研究所 腫瘍制御学分野

    • URL

      https://cancer-c.pref.aichi.jp/site/folder5/1331.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 愛知県がんセンター研究所 腫瘍制御学分野

    • URL

      https://cancer-c.pref.aichi.jp/cancer-center/ri/01bumon/06shuyo_uirusu/03member.html

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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