Molecular Mechanisms of podosome formation

足体形成的分子机制

• 批准号: 20790255
• 负责人: OIKAWA Tsukasa
• 金额: $ 2.16万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790255/
• 关键词: がん; 浸潤; イノシトールリン脂質

The great majority of cancers occur in epithelial tissues, yielding carcinomas. Given that epithelial cells are on the basement membrane underneath, they must degrade it to travel to distant sites. To initiate the invasion process, they must make contact with the extracellular matrices (ECM). Thus, the cell-matrix interactions must be one of the triggers that allow cancer cells to invade. To penetrate into the ECM, actin-rich adhesion structures called invadopodia or podosomes is thought to play pivotal roles for degrading it. I have studied the mechanism of invadopodium/podosome formation in Src-transformed NIH3T3 cells. In this study, based on the results of RNAi, identification of binding proteins by mass spectrometry, protein interaction and live-cell imaging analysis, I have established a stepwise mechanism for invadopodium formation. Invadopodia initiate from focal adhesions (FAs) due to changes in the phosphorylation status of proteins and in the composition of phosphoinositides on the plasma membrane. The onset of actin polymerization is triggered by PI(3,4)P2 production and Tks5 recruitment followed by N-WASP accumulation. This step involves intricate interactions of Tks5 with both PI(3,4)P2 and Grb2 at FAs

绝大多数癌症发生在上皮组织中，产生癌。由于上皮细胞位于基底膜上，它们必须降解基底膜才能到达远处。为了启动入侵过程，它们必须与细胞外基质（ECM）接触。因此，细胞-基质相互作用一定是允许癌细胞侵入的触发因素之一。要渗透到ECM，肌动蛋白丰富的粘附结构称为invadopodia或podosomes被认为是发挥关键作用降解it. I已研究的机制invadopodium/podosomes形成Src转化的NIH 3 T3细胞。在这项研究中，基于RNAi的结果，通过质谱鉴定结合蛋白，蛋白质相互作用和活细胞成像分析，我已经建立了一个逐步的机制，invadopodium形成。侵入伪足起源于粘着斑（FA），粘着斑是由于蛋白质磷酸化状态和质膜上磷酸肌醇组成的变化引起的。肌动蛋白聚合的开始由PI（3，4）P2产生和Tks 5募集随后由N-WASP积累触发。该步骤涉及Tks 5与PI（3，4）P2和Grb 2在FA处的复杂相互作用

项目成果

PtdIns(3,4)P2 instigates focal adhesions to generate podosomes

• DOI: 10.4161/cam.3.2.7510
• 发表时间: 2009-04-01
• 期刊: CELL ADHESION & MIGRATION
• 影响因子: 3.2
• 作者: Oikawa, Tsukasa;Takenawa, Tadaomi
• 通讯作者: Takenawa, Tadaomi

Sequential signals toward podosome formation in NIH-src cells.

• DOI: 10.1083/jcb.200801042
• 发表时间: 2008-07-14
• 期刊: The Journal of cell biology
• 作者: Oikawa T;Itoh T;Takenawa T
• 通讯作者: Takenawa T

破骨細胞と骨芽細胞の極性決定

破骨细胞和成骨细胞极性测定

• 发表时间: 2009
• 作者: Yoshifumi Takahata*;Takeshi Takarada*;Mika Iemata;Tomomi Yamamoto;Yukary Nakamura;Ayumi Kodama;Yukio Yoneda;及川司
• 通讯作者: 及川司