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Multimodal imaging analysis of oral cancer cells focused on lysosomes

Research Project

Project/Area Number 21K10047
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionNagasaki University

Principal Investigator

Sumi Tadateru  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (80284701)

Co-Investigator(Kenkyū-buntansha) 筑波 隆幸  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
山口 優  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (50823308)
門脇 知子  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (70336080)
Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords口腔癌細胞 / リソソーム / イメージング / マルチモーダルイメージング / カテプシンK
Outline of Research at the Start

癌細胞が浸潤と転移を起こすのは、リソソームが細胞外へ分泌される事と深い相関がある。近年、我々はリソソーム性タンパク質の発現レベルを抑制すると浸潤と転移が低下する事を示した。そこで本研究では、口腔癌においてリソソームがどのように細胞や生体の機能に影響を与えるかを様々なイメージングを用いて明らかにする。複数の方法を組み合わせて行うことでリソソームからの分泌がいつ、どのように起こるのかを分子から細胞、さらに個体レベルへと、ミクロからマクロレベルの解析を行う。本研究は不明な点が多く残されていたリソソームによる癌細胞の浸潤と転移について新しい知見を与えてくれるものである。

Outline of Final Research Achievements

Cancer cell invasion and metastasis are closely correlated with the extracellular secretion of lysosomes. Recently, we have shown that suppressing the expression level of lysosomal proteins reduces invasion and metastasis. In this study, we aimed to clarify how lysosomes affect cellular and biological functions in oral cancer using various imaging techniques. By combining multiple methods, we performed macro- and micro-level analyses of when and how secretion from lysosomes occurs, from the molecular to the cellular and individual levels. This study uses various imaging analyses to elucidate the invasion and metastasis of cancer cells by lysosomes, which has remained largely unknown.

Academic Significance and Societal Importance of the Research Achievements

本研究では口腔扁平上皮癌細胞からのリソソームのイメージングを行うことで、癌細胞からのリソソームの機能やリソソーム性酵素の分泌パターンを明らかにすることができる。この知見は、(1)癌の浸潤・転移を分子レベルで解明することができる、(2)細胞外基質の分解の抑制を制御する事ができること、(3)最終的に浸潤と転移を制御できる新たな治療法の開発に極めて重要な知見を得ることができると予想される。

Report

(5 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (36 results)

All 2024 2023 2022 2021

All Journal Article (19 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 19 results,  Open Access: 19 results) Presentation (16 results) Book (1 results)

  • [Journal Article] Transcriptomic Characterization Reveals Mitochondrial Involvement in Nrf2/Keap1-Mediated Osteoclastogenesis2024

    • Author(s)
      Sakai Eiko、Tsukuba Takayuki
    • Journal Title

      Antioxidants

      Volume: 13 Issue: 12 Pages: 1575-1575

    • DOI

      10.3390/antiox13121575

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired Development of Collagen Antibody-Induced Arthritis in Rab44-Deficient Mice2024

    • Author(s)
      Yamaguchi Yu、Kadowaki Tomoko、Sakai Eiko、Noguromi Mayuko、Oyakawa Shun、Tsukuba Takayuki
    • Journal Title

      Biomedicines

      Volume: 12 Issue: 11 Pages: 2504-2504

    • DOI

      10.3390/biomedicines12112504

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dennd2c Negatively Controls Multinucleation and Differentiation in Osteoclasts by Regulating Actin Polymerization and Protrusion Formation2024

    • Author(s)
      Koyanagi Yu、Sakai Eiko、Yamaguchi Yu、Farhana Fatima、Taira Yohsuke、Okamoto Kuniaki、Murata Hiroshi、Tsukuba Takayuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 25 Issue: 21 Pages: 11479-11479

    • DOI

      10.3390/ijms252111479

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy Regulator Rufy 4 Promotes Osteoclastic Bone Resorption by Orchestrating Cytoskeletal Organization via Its RUN Domain2024

    • Author(s)
      Sakai Eiko、Saito Minoru、Koyanagi Yu、Takayama Yoshitsugu、Farhana Fatima、Yamaguchi Yu、Tsukuba Takayuki
    • Journal Title

      Cells

      Volume: 13 Issue: 21 Pages: 1766-1766

    • DOI

      10.3390/cells13211766

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Herbal medicine Ninjinyoeito inhibits RANKL-induced osteoclast differentiation and bone resorption activity by regulating NF-κB and MAPK pathway2024

    • Author(s)
      Htike Kaung、Yoshida Kunihiro、Eguchi Takanori、Takebe Katsuki、Li Xueming、Qu Yaxin、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Journal of Oral Biosciences

      Volume: 66 Issue: 4 Pages: 49-57

    • DOI

      10.1016/j.job.2024.09.007

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RASEF/Rab45 regulates the formation and sorting of zymogen granules and secretion of digestive enzymes by pancreatic acinar cells2024

    • Author(s)
      Sato Keiko、Kadowaki Tomoko、Takenaka Mamoru、Konishi Mayo、Ando Miyabi、Onodera Takae、Tsukuba Takayuki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1870 Issue: 7 Pages: 167310-167310

    • DOI

      10.1016/j.bbadis.2024.167310

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44 negatively regulates myoblast differentiation by controlling fusogenic protein transport and mTORC1 signaling2023

    • Author(s)
      Tanimoto Ayuko、Yamaguchi Yu、Kadowaki Tomoko、Sakai Eiko、Oyakawa Shun、Ono Yusuke、Yoshida Noriaki、Tsukuba Takayuki
    • Journal Title

      Journal of Cellular Biochemistry

      Volume: 124 Issue: 10 Pages: 1486-1502

    • DOI

      10.1002/jcb.30457

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44 deficiency accelerates recovery from muscle damage by regulating mTORC1 signaling and transport of fusogenic regulators2023

    • Author(s)
      Oyakawa Shun、Yamaguchi Yu、Kadowaki Tomoko、Sakai Eiko、Noguromi Mayuko、Tanimoto Ayuko、Ono Yusuke、Murata Hiroshi、Tsukuba Takayuki
    • Journal Title

      Journal of Cellular Physiology

      Volume: 238 Issue: 10 Pages: 2253-2266

    • DOI

      10.1002/jcp.31082

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abr, a Rho-regulating protein, modulates osteoclastogenesis by enhancing lamellipodia formation by interacting with poly(ADP-ribose) glycohydrolase2023

    • Author(s)
      Farhana Fatima、Sakai Eiko、Koyanagi Yu、Yamaguchi Yu、Alam Mohammad Ibtehaz、Okamoto Kuniaki、Tsukuba Takayuki
    • Journal Title

      Molecular Biology Reports

      Volume: 50 Issue: 9 Pages: 7557-7569

    • DOI

      10.1007/s11033-023-08690-0

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transposon mutagenesis and genome sequencing identify two novel, tandem genes involved in the colony spreading of Flavobacterium collinsii, isolated from an ayu fish, Plecoglossus altivelis2023

    • Author(s)
      Kondo Yoshio、Ohara Kenichi、Fujii Ryoji、Nakai Yudai、Sato Chikara、Naito Mariko、Tsukuba Takayuki、Kadowaki Tomoko、Sato Keiko
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 13 Pages: 01-16

    • DOI

      10.3389/fcimb.2023.1095919

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy2023

    • Author(s)
      Noguromi Mayuko、Yamaguchi Yu、Sato Keiko、Oyakawa Shun、Okamoto Kuniaki、Murata Hiroshi、Tsukuba Takayuki、Kadowaki Tomoko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 2 Pages: 994-994

    • DOI

      10.3390/ijms24020994

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab34 plays a critical role as a bidirectional regulator of osteoclastogenesis2022

    • Author(s)
      Feng Yunxia、Tran Manh Tien、Lu Yanyin、Htike Kaung、Okusha Yuka、Sogawa Chiharu、Eguchi Takanori、Kadowaki Tomoko、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Cell Biochemistry and Function

      Volume: 40 Issue: 3 Pages: 263-277

    • DOI

      10.1002/cbf.3691

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coronin1C is a GDP-specific Rab44 effector that controls osteoclast formation by regulating cell motility in macrophages.2022

    • Author(s)
      Yu Yamaguchi, Tomoko Kadowaki, Nozomi Aibara, Kaname Ohyama, Kuniaki Okamoto, Eiko Sakai and Takayuki Tsukuba
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 23 Issue: 12 Pages: 6619-6619

    • DOI

      10.3390/ijms23126619

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HSP90 drives the Rab11a-mediated vesicular transport of the cell surface receptors in osteoclasts2022

    • Author(s)
      Tran MT, Okusha Y, Feng Y, Sogawa C, Eguchi T, Kadowaki T, Sakai E, Tsukuba T, Okamoto K
    • Journal Title

      Cell Biochem Funct

      Volume: 40(8) Issue: 8 Pages: 838-855

    • DOI

      10.1002/cbf.3745

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liquid-phase ASEM imaging of cellular and structural details in cartilage and bone formed during endochondral ossification: Keap1-deficient osteomalacia2021

    • Author(s)
      Sakai E, Sato M, Memtily N, Tsukuba T, Sato C.
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 5722-5722

    • DOI

      10.1038/s41598-021-84202-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel role of HSP90 in regulating osteoclastogenesis by abrogating Rab11b-driven transport2021

    • Author(s)
      Tran Manh Tien、Okusha Yuka、Feng Yunxia、Sogawa Chiharu、Eguchi Takanori、Kadowaki Tomoko、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1868 Issue: 10 Pages: 119096-119096

    • DOI

      10.1016/j.bbamcr.2021.119096

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Large Rab GTPases: Novel Membrane Trafficking Regulators with a Calcium Sensor and Functional Domains2021

    • Author(s)
      Tsukuba Takayuki、Yamaguchi Yu、Kadowaki Tomoko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 14 Pages: 7691-7691

    • DOI

      10.3390/ijms22147691

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44 isoforms similarly promote lysosomal exocytosis, but exhibit differential localization in mast cells.2021

    • Author(s)
      Kadowaki T, Yamaguchi Y, Ogawa K, Tokuhisa M, Okamoto K, Tsukuba T.
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 4 Pages: 1165-1185

    • DOI

      10.1002/2211-5463.13133

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis2021

    • Author(s)
      Mae Megumi、Alam Mohammad Ibtehaz、Yamashita Yasunori、Ozaki Yukio、Higuchi Kanako、Ziauddin S. M.、Montenegro Raudales Jorge Luis、Sakai Eiko、Tsukuba Takayuki、Yoshimura Atsutoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 22 Pages: 12434-12434

    • DOI

      10.3390/ijms222212434

    • NAID

      120007186852

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 人参養栄湯はNF-κB 経路を介して破骨細胞分化や骨吸収を抑制する2024

    • Author(s)
      Kaung Htike、吉田 国弘、江口 傑徳、武部 克希、坂井 詠子、筑波 隆幸、岡元 邦彰
    • Organizer
      第66回歯科基礎医学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 腺がん細胞におけるRASEF 発現の影響2024

    • Author(s)
      武中 守、小野寺 貴恵、佐藤 啓子、筑波 隆幸、門脇 知子
    • Organizer
      第66回歯科基礎医学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Dennd2c はマクロファージの突起形成を調節することにより破骨細胞の分化と多核化を負に制御する2024

    • Author(s)
      小栁 悠、坂井 詠子、山口 優、筑波 隆幸
    • Organizer
      第66回歯科基礎医学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Porphyromonas gingivalis 新規オペロンに存在するOmp 様タンパク質の構造解析と役割2024

    • Author(s)
      Chen Yujiang、武部 克希、佐藤 啓子、中山 真彰、加島 佳奈、Zhang Mingzheng 、岡元 邦彰、門脇  知子、大原  直也
    • Organizer
      第66回歯科基礎医学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Porphyromonas gingivalis の病原因子分泌機構2024

    • Author(s)
      佐藤 啓子、近藤 好夫、佐藤 主税、小野寺 貴恵、門 脇 知子
    • Organizer
      第66回歯科基礎医学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Rab44は筋衛星細胞におけるmTORC1シグナル伝達と融合制御因子の輸送の調節により筋再生を負に制御する2023

    • Author(s)
      親川駿、山口優,門脇知子,坂井詠子, 野黒美麻由子, 谷本あゆ子, 筑波 隆幸
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Research-status Report
  • [Presentation] Rab44はmTORC1シグナルを制御することで筋芽細胞の分化を負に制御する2023

    • Author(s)
      谷本 あゆ子、山口 優,門脇 知子,坂井 詠子, 親川 駿, 筑波 隆幸
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Research-status Report
  • [Presentation] Rufy4のRUNドメイン欠失変異体は糸状仮足形成を促進し破骨細胞の骨吸収を抑制する2023

    • Author(s)
      坂井 詠子, 小栁 悠, Farhana Fatima, 山口 優,筑波 隆幸
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Research-status Report
  • [Presentation] Dennd2cは破骨細胞分化を負に制御する2023

    • Author(s)
      小栁 悠、坂井 詠子、山口 優、Farhana Fatima、平 曜輔、村田比呂司、筑波 隆幸
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Research-status Report
  • [Presentation] Rab44はコラーゲン抗体誘発性関節炎において炎症反応を制御する2023

    • Author(s)
      山口 優,門脇 知子,坂井 詠子,野黒美 麻由子,親川 駿, 日浅 匠,馬渡 遥香,筑波 隆幸
    • Organizer
      第46回 日本分子生物学会年会
    • Related Report
      2023 Research-status Report
  • [Presentation] Rab44タンパク質による炎症応答制御機構2022

    • Author(s)
      門脇知子、山口 優、佐藤啓子、筑波隆幸
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 高分子量Rabタンパク質が制御する筋芽細胞から筋管への分化機構2022

    • Author(s)
      谷本 あゆ子,山口 優,門脇 知子,親川 駿, 坂井 詠子,小野 悠介, 吉田 教明,筑波 隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Coronin1CはGDP特異的Rab44エフェクターでありマクロファージの細胞運動を調節することで破骨細胞形成を制御する2022

    • Author(s)
      山口 優,門脇 知子,相原 希美,大山 要,岡元 邦彰,坂井 詠子,筑波 隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 高分子量Rabタンパク質による筋衛星細胞と筋形成過程に及ぼす影響2022

    • Author(s)
      親川駿、山口優,門脇知子,谷本あゆ子, 坂井詠子,村田比呂司、筑波隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Rufy4はRUNドメインを介して破骨細胞による骨吸収を制御する2022

    • Author(s)
      坂井 詠子, Farhana Fatima, 小栁 悠, 山口 優,筑波 隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 金属アレルギーでの高分子量Gタンパク質Rab44の役割2022

    • Author(s)
      野黒美麻由子、山口優、佐藤啓子、村田比呂司、筑波隆幸、門脇知子
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Book] 現代歯科薬理学 第7版2024

    • Author(s)
      鈴木 邦明、戸苅 彰史、青木 和広、兼松 隆、筑波 隆幸、八田 光世
    • Total Pages
      416
    • Publisher
      医歯薬出版
    • ISBN
      9784263456774
    • Related Report
      2023 Research-status Report

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Published: 2021-04-28   Modified: 2026-01-16  

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