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細胞膜分子動態数理モデリングによるがん悪性化メカニズムの解明

Research Project

Project/Area Number 15KT0016
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Mathematical Sciences in Search of New Cooperation
Research InstitutionOsaka University

Principal Investigator

鈴木 貴  大阪大学, 基礎工学研究科, 教授 (40114516)

Co-Investigator(Kenkyū-buntansha) 川崎 秀二  岩手大学, 理工学部, 准教授 (10282922)
村上 善則  東京大学, 医科学研究所, 教授 (30182108)
越川 直彦  地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所がん生物学部, 部長 (70334282)
Project Period (FY) 2015-07-10 – 2017-03-31
Project Status Discontinued (Fiscal Year 2016)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords数理腫瘍学 / 数理モデリング / 細胞分子動態 / 細胞接着 / ECM分解 / 細胞膜分子 / 骨代謝 / 薬剤耐性 / 細胞内信号伝達 / 動的平衡 / 遺伝子
Outline of Annual Research Achievements

がん細胞悪性化および悪性伝播の分子レベルのメカニズムを,生物医学の問題として解明する事を目指した.その結果NFkBによるシグナル伝達, Metによる薬剤耐性獲得機序, 骨代謝モデルにおける動的平衡崩壊のメカニズムを理論的に明確に解明することができた. 基本的方法としては,数理モデリングという数理解析法の適用である.がん細胞悪性伝搬の分子レベルでのメカニズムは極めて複雑で, これまで生物医学の問題として難題と言われてきたが,生物医学的定性的解析と数理科学的定量的解析の相互フィードバックにより僅かずつ歩を進めた.従来は,細胞核での遺伝子変異を調べようとする,遺伝子解析が主な研究対象であったが,本課題では,最新の研究成果を踏まえて,がん細胞悪性化および悪性伝播を引起こすシグナル伝達系を対象とし, 数学的方法で上記の騎乗を解明した.さらにデータを用いて,細胞膜上で受容体が受けたシグナルが細胞膜内分子へ伝達され、細胞膜内で複数のシグナル伝達系統のクロストークを経て悪性化したシグナルが細胞膜へ再びフィードバック遡上する経路(下流分子経路),および,遡上してきたシグナルが細胞膜上に存在する隣接細胞との接着剥離分子を通じて悪性を伝播してしまう経路(上流経路)を数理モデリングし, さらに数学解析を用いて生命動態の本質を解明することを試みた.これらの試みによって, 少数のパラメータと次元解析によってモデルを定量化すること, 生命動態を空間的に分布したイベントとして記述したうえで, 揺らぎを含む有効な計算法などの新しい数理的手法も開発した.

Report

(2 results)
  • 2016 Annual Research Report
  • 2015 Research-status Report
  • Research Products

    (25 results)

All 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] ボルドー大学(フランス)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] セントアンドリュース大学(英国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] ヴァンダービルト大学(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Chemotaxis with quadratic dissipation and logistic source2016

    • Author(s)
      Evangelos Latos and Takashi Suzuki
    • Journal Title

      Adv. Math. Sci. Appl.

      Volume: 25 Pages: 203-223

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Enhancement of BGA-void defect detection in poor contrast X-ray images using conformal mapping2016

    • Author(s)
      S. Nuanprasert, K. Lee, A. Murid, S. Baba, T. Suzuki
    • Journal Title

      J. ICIC Epress Letters B

      Volume: 7 Pages: 105-110

    • NAID

      40020834976

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] あるN分子パスウェイネットワークの数理モデリングと数学解析2016

    • Author(s)
      板野景子, 鈴木貴
    • Journal Title

      日本応用数理学会論文誌

      Volume: 26

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-fitting2015

    • Author(s)
      Sakurai-Yageta, M., Maruyama,T., Suzuki, T., Ichikawa, K., and Murakami, Y.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 3 Pages: 0116637-0116637

    • DOI

      10.1371/journal.pone.0116637

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein. Cancer Res2015

    • Author(s)
      Koshikawa N, Hoshino D, Taniguchi H, Minegishi T, Tomari T, Nam SO, Aoki M, Sueta T, Nakagawa T, Miyamoto S, Nabeshima K, Weaver AM, Seiki M
    • Journal Title

      Cancer Res

      Volume: 75(16) Issue: 16 Pages: 3327-39

    • DOI

      10.1158/0008-5472.can-14-2798

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Directional cell movement through tissues is controlled by exosome secretion2015

    • Author(s)
      Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 7164-7164

    • DOI

      10.1038/ncomms8164

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer2015

    • Author(s)
      Young CD, Zimmerman LJ, Hoshino D, Formisano L, Hanker AB, Gatza ML, Morrison MM, Moore PD, Whitwell CA, Dave B, Stricker T, Bhola NE, Silva GO, Patel P, Brantley-Sieders DM, Levin M, Horiates M, Palma NA, Wang K, Stephens PJ, Perou CM, Weaver AM, O'Shaughnessy JA, Chang JC, Park BH, Liebler DC, Cook RS, Arteaga CL
    • Journal Title

      Mol Cell Proteomics

      Volume: 14(7) Issue: 7 Pages: 1959-76

    • DOI

      10.1074/mcp.m115.049783

    • Related Report
      2015 Research-status Report
  • [Journal Article] Response of head and neck squamous cell carcinoma cells carrying PIK3CA mutations to selected targeted therapies2015

    • Author(s)
      Wirtz ED, Hoshino D, Maldonado AT, Tyson DR, Weaver AM
    • Journal Title

      JAMA Otolaryngol Head Neck Surg

      Volume: 141(6) Issue: 6 Pages: 543-9

    • DOI

      10.1001/jamaoto.2015.0471

    • Related Report
      2015 Research-status Report
  • [Journal Article] Urinary laminin-γ2 is a novel biomarker of non-muscle invasive urothelial carcinoma2015

    • Author(s)
      Kamada M, Koshikawa N, Minegishi T, Kawada C, Karashima T, Shuin T, & Seiki M
    • Journal Title

      Cancer Sci

      Volume: 106(12) Pages: 1730-7

    • Related Report
      2015 Research-status Report
  • [Journal Article] Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein2015

    • Author(s)
      Koshikawa N, Hoshino D, Taniguchi H, Minegishi T, Tomari T, Nam SO, Aoki M, Sueta T, Nakagawa T, Miyamoto S, Nabeshima K, Weaver AM, Seiki M
    • Journal Title

      Cancer Res

      Volume: 75(16) Pages: 3327-39

    • Related Report
      2015 Research-status Report
  • [Journal Article] Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma2015

    • Author(s)
      Kikuchi K, Noguchi A, Kasajima R, Miyagi Y, Hoshino D, Koshikawa N, Kubota A, Yokose T, Takano Y
    • Journal Title

      Tumour Biol

      Volume: 36(10) Pages: 7865-72

    • Related Report
      2015 Research-status Report
  • [Presentation] Comprehensive analysis of the pro-oncogenic signaling induced by proteolysis of MT1-MMP substrate in vivo2016

    • Author(s)
      Koshikawa, N
    • Organizer
      The First JSPS Core-to-Core Seminar: Establishing International Research Network of Mathematical Oncology
    • Place of Presentation
      大和高原ボスコヴィラ(奈良県・奈良市)
    • Year and Date
      2016-03-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Mathematical analysis of the dynamics of CADM1 and its role in the MET-driven resistance against EGFR-TKI in lung adenocarcinoma2016

    • Author(s)
      Takeshi Ito, Mika Sakurai-Yageta, Takehiro Tsuchiya, Shuji Kawasaki, Motoi Ohba, Kazuhisa Ichikawa, Takashi Suzuki, Yoshinori Murakami
    • Organizer
      The First JSPS Core-to-Core Seminar: Establishing International Research Network of Mathematical Oncology
    • Place of Presentation
      大和高原ボスコヴィラ(奈良県・奈良市)
    • Year and Date
      2016-03-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 次元解析を用いた薬剤耐性モデリング2016

    • Author(s)
      鈴木貴
    • Organizer
      日本細胞生物学会大会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 数理腫瘍学の方法-骨代謝モデルにおける動的平衡の崩壊2015

    • Author(s)
      鈴木貴
    • Organizer
      実領域における常微分方程式の定性的研究
    • Place of Presentation
      京都大学数理解析研究所(京都府・京都市)
    • Year and Date
      2015-11-10
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Mathematical oncology and applications2015

    • Author(s)
      T. Suzuki
    • Organizer
      Forum Math-for-Industry 2015
    • Place of Presentation
      九州大学マスフォアインダストリ研究所(福岡県・福岡市)
    • Year and Date
      2015-10-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] From systems biology to mathematical modeling2015

    • Author(s)
      T. Suzuki
    • Organizer
      Vanderbilt University CQS Fall Retreat
    • Place of Presentation
      Vanderbilt University, Nashville, USA
    • Year and Date
      2015-10-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] FRAPとexponential curve-fitting の組み合わせ解析による細胞接着分子CADM1複合体の動的制御の解明2015

    • Author(s)
      伊東剛、桜井美佳、斎藤杏里、丸山智子、市川一寿、村上善則
    • Organizer
      日本応用数理学会2015年度年会
    • Place of Presentation
      金沢大学(石川県・金沢市)
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 数理腫瘍学の方法-細胞分子モデリング2015

    • Author(s)
      鈴木貴
    • Organizer
      非線型現象のモデルに潜む未踏破数理構造の研究-基礎理論と応用の協働
    • Place of Presentation
      京都大学数理解析研究所(京都府・京都市)
    • Year and Date
      2015-07-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] Methods of Mathematical Cell Biology2016

    • Author(s)
      T. Suzuki
    • Total Pages
      150
    • Publisher
      Springer Verlag
    • Related Report
      2016 Annual Research Report
  • [Book] 数理医学入門2015

    • Author(s)
      鈴木貴
    • Total Pages
      258
    • Publisher
      共立出版
    • Related Report
      2015 Research-status Report
  • [Remarks] 大阪大学大学院 基礎工学研究科システム創成専攻数理科学領域 鈴木貴研究室

    • URL

      http://www.sigmath.es.osaka-u.ac.jp/suzuki/index.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-07-14   Modified: 2022-08-29  

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