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

通过细胞膜分子动力学数学建模阐明癌症恶性机制

• 批准号: 15KT0016
• 负责人: 鈴木 貴
• 金额: $ 11.15万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2015
• 资助国家: 日本
• 起止时间: 2015-07-10 至 2017-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15KT0016/
• 关键词: 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

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.

The biomedical problem solving of the biomedical problem is to understand the target of the disease. The results showed that the NFkB was successful, the Met was able to gain tolerance, and the bone agent was responsible for the equilibrium collapse of the disease. The clear understanding of the theory of the theory of mechanical collapse. The basic methods are: mathematical analysis, mathematical The qualitative analysis of biomedical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative analysis of mathematical science, the quantitative The method of mathematics is the mathematical method to explain the problem. The receptor on the cell membrane is affected by the expression of the molecules in the cell membrane and the number of molecules in the cell membrane. The system is sensitive to the expression of the receptor on the cell membrane, the molecule on the cell membrane, the molecule on the cell membrane, the receptor on the cell membrane. On the cell membrane, there is a cell connection, and then the molecules are separated from each other. The mathematical analysis is used to understand the dynamics of life. A small number of data sets are analyzed in terms of quantitative analysis, the distribution in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the distribution of data in the space of life dynamics, the

项目成果

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

FRAP与指数曲线拟合联合分析阐明细胞粘附分子CADM1复合物的动态调节

• 发表时间: 2015
• 作者: 伊東剛;桜井美佳;斎藤杏里;丸山智子;市川一寿;村上善則
• 通讯作者: 村上善則

セントアンドリュース大学(英国)

圣安德鲁斯大学（英国）

Directional cell movement through tissues is controlled by exosome secretion.

• DOI: 10.1038/ncomms8164
• 发表时间: 2015-05-13
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Sung, Bong Hwan;Ketova, Tatiana;Hoshino, Daisuke;Zijlstra, Andries;Weaver, Alissa M.
• 通讯作者: Weaver, Alissa M.

Mathematical analysis of the dynamics of CADM1 and its role in the MET-driven resistance against EGFR-TKI in lung adenocarcinoma.

CADM1 动态及其在 MET 驱动的肺腺癌 EGFR-TKI 耐药中的作用的数学分析。

• 发表时间: 2016
• 作者: Ito T;Sakurai-Yageta M;Tsuchiya T;Kawasaki S;Ohba M;Ichikawa K;Suzuki T;Murakami Y.
• 通讯作者: Murakami Y.

Comprehensive analysis of the pro-oncogenic signaling induced by proteolysis of MT1-MMP substrate in vivo

体内MT1-MMP底物蛋白水解诱导的促癌信号传导综合分析

• 发表时间: 2016
• 作者: Koshikawa;N
• 通讯作者: N