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Development of novel intervening approaches to cancer progression by comprehensive analyses of interactions between cell adhesion molecules

Research Project

Project/Area Number 20K21539
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Murakami Yoshinori  東京大学, 医科学研究所, 教授 (30182108)

Co-Investigator(Kenkyū-buntansha) 伊東 剛  東京大学, 医科学研究所, 助教 (20733075)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords免疫グロブリンスーパーファミリータンパク質 / がんの浸潤、転移 / 免疫チェックポイント / がん浸潤・転移 / 分子間結合 / 糖鎖 / 腫瘍免疫
Outline of Research at the Start

炎症・免疫、感染、がん転移等を細胞接着の異常と捉え、鍵となる分子相互作用を同定するために、時空間的相互作用の多様性に富む免疫グロブリン・スーパーファミリー (IgSF) 分子群を標的とクローニングし、細胞外ドメインの物理化学的分子間相互作用、生物工学的分子・細胞間相互作用を検出可能な実験系を構築する。これを用いて、生理・病理活性の鍵となる分子相互作用を同定し、意義を解明し、阻害による病態修飾を図る。具体的には、IgSF分子検索系の構築、腫瘍免疫、がん転移、ウイルス感染の鍵となる分子相互作用の同定と解析、多彩な細胞接着分子病の解明を行う。

Outline of Final Research Achievements

Immunoglobulin superfamily molecules (IgSFs), one of the largest family proteins in vertebrates, are involved in a variety of cell-cell and cell-substrate interaction. To identify novel bindings of these IgSFs will provide a fundamental knowledge of biological phenomena triggered by cell-cell interaction. The information also leads to novel understanding of various diseases caused by abnormal cell-cell interaction, including tumor invasion/metastasis and tumor immunity. In this study, we obtained following results and outcomes.
1.Comprehensive screening of IgSF interaction of more than 300 molecules was performed by physico-chemical analysis. 2.Key molecules involved in invasion of T-cell lymphomas and in novel immune checkpoints were identified. 3.Functional assays of these key molecules in cell biological approaches or in animal model analysis were performed to obtain promising results to support that these molecules are possible molecular targets for cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

IgSF分子間結合は様々な細胞間接着に関わり、その異常はがんの浸潤・転移、腫瘍免疫(免疫チェックポイント)などに関わることが知られている。しかし、IgSF分子間結合は現時点ではゲノム、アミノ酸配列からは予測できず、個々の分子による実験的検証が唯一の解析手法である。本研究では、分子クローニング、ALPHA, SPR 等の物理化学的手法による検索法を確立した。さらにがんの浸潤、転移の鍵分子を同定し、また免疫チェックポインチの新規鍵分子対を同定した。これらは、がんの新規治療の開発にも応用される重要で社会的意義も兼ね備えた研究成果である。

Report

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

    (18 results)

All 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (9 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results) Remarks (1 results)

  • [Int'l Joint Research] Khon Kaen University, School of Medicine(タイ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Khon Kaen University, School of Medicne(タイ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Trans-homophilic interaction of CADM1 promotes organ infiltration of T-cell lymphoma by adhesion to vascular endothelium.2022

    • Author(s)
      Kasai Y, Gan SP, Funaki T, Ohashi-Kumagai Y, Tominaga M, Shiu S-J, Suzuki D, Matsubara D, Sakamoto T, Sakurai-Yageta M, Ito T, Murakami Y.
    • Journal Title

      Cancer Science

      Volume: in press Issue: 5 Pages: 1-2

    • DOI

      10.1111/cas.15307

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer.2022

    • Author(s)
      Akashi K, Sakai T, Fukuoka O, Saito Y, Yoshida M, Ando M, Ito T, Murakami Y, Yamasoba T.
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 572-572

    • DOI

      10.1038/s41598-021-04307-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating tumor DNA harboring the BRAF V600E mutation may predict poor outcomes of primary papillary thyroid cancer patients.2021

    • Author(s)
      Sato A, Tanabe M, Tsuboi Y, Niwa T, Shinozaki-Ushiku A, Seto Y, Murakami Y.
    • Journal Title

      Thyroid

      Volume: 31 Issue: 12 Pages: 1822-1828

    • DOI

      10.1089/thy.2021.0267

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CADM1 promotes malignant features of small-cell lung cancer by recruiting 4.1R to the plasma membrane2021

    • Author(s)
      Funaki Toko、Ito Takeshi、Tanei Zen-ichi、Goto Akiteru、Niki Toshiro、Matsubara Daisuke、Murakami Yoshinori
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 534 Pages: 172-178

    • DOI

      10.1016/j.bbrc.2020.11.121

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Short somatic alterations at the site of copy number variation in breast cancer2020

    • Author(s)
      Murakami Fumi、Tsuboi Yumi、Takahashi Yuka、Horimoto Yoshiya、Mogushi Kaoru、Ito Takeshi、Emi Mitsuru、Matsubara Daisuke、Shibata Tatsuhiro、Saito Mitsue、Murakami Yoshinori
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 1 Pages: 444-453

    • DOI

      10.1111/cas.14630

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CADM1 suppresses c-Src activation by binding with Cbp on membrane lipid rafts and intervenes colon carcinogenesis2020

    • Author(s)
      Tsuboi Yumi、Oyama Masaaki、Kozuka-Hata Hiroko、Ito Akihiko、Matsubara Daisuke、Murakami Yoshinori
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 3 Pages: 854-860

    • DOI

      10.1016/j.bbrc.2020.05.103

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Comprehensive analysis of human cancer on the basis of cohort and biobanks.2021

    • Author(s)
      Yoshinori Murakami.
    • Organizer
      The 80th Annual Meeting of Japanese Cancer Association
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The extracellular fragments of a CADM1 variant isoform can be a serum marker for small-cell lung cancer.2021

    • Author(s)
      Takeshi Ito, Daisuke Matsubara, Toko Funaki, Kenji Tamura, Takahide Nagase, Yoshinori Murakami.
    • Organizer
      The 80th Annual Meeting of Japanese Cancer Association
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CADM1 promotes malignant features of small-cell lung cancer by recruiting 4.1R to the plasma membrane.2021

    • Author(s)
      Toko Funaki, Takeshi Ito, Yoshinori Murakami.
    • Organizer
      The 80th Annual Meeting of Japanese Cancer Association
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CADM1 promotes organ infiltration of adult T-cell leukemia/lymphoma (ATL) cells.2021

    • Author(s)
      Yutaka Kasai, Takeharu Sakamoto, Takeshi Ito, Yoshinori Murakami.
    • Organizer
      The 80th Annual Meeting of Japanese Cancer Association
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Biobank Network for Promotion of Utilization of Biobank toward Realization of Genomic Medicine in Japan.2021

    • Author(s)
      Ogishima S, Murakami Y, Goto Y, Morisaki M, Imoto S, Matsuda K, Hirata M, Yokota H,
    • Organizer
      Annual Meeting of International Society for Biological and Environmental Repositories 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cohorts and biobanks, essential resources for cancer research and medicine.2021

    • Author(s)
      Murakami Y
    • Organizer
      Khon Kaen University and IMSUT International Mini-Symposium supported by the International Joint Usage-Joint Research Program
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cohorts and biobanks as essential resources for accelerating precision medicine in cancer.2020

    • Author(s)
      Yoshinori Murakami, Koichi Matsuda, Takayuki Morisaki, Yukihide Momozawa, Toshiki Watanabe, Yataro Daigo, Kenji Wakai.
    • Organizer
      The 79th Annual Meeting of Japanese Cancer Association, Core Symposium.
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Novel mechanisms of EGFR-TKI resistance and clonal evolution of lung adenocarcinoma by over expression of a cell adhesion molecule, CADM1.2020

    • Author(s)
      Tsuchiya T, Kuwano H, Ito T, Nagata M, Kawai T, Matsubara D, Okamoto I, Tamura K, Nakajima J, Oba M, Murakami Y.
    • Organizer
      AACR Special Conference, Tumor Heterogeneity
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a novel serum marker for detecting small cell lung cancer by targeting a Cell Adhesion Molecule 1 (CADM1).2020

    • Author(s)
      Ito T, Funaki T, Iwanari H, Tanaka G, Nagase T, Hamakubo T, Murakami Y.
    • Organizer
      2020 Annual Meeting of the American Association for Cancer Research.
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Remarks] 人癌病因遺伝子分野におけるがん研究

    • URL

      https://www.ims.u-tokyo.ac.jp/hitogan/index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

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