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，从而产生癌症。鉴于上皮细胞位于基底膜上，它们必须将其降解，才能移动到远处。为了启动侵袭过程，它们必须与细胞外基质(ECM)接触。因此，细胞-基质的相互作用一定是允许癌细胞入侵的触发因素之一。为了穿透细胞外基质，富含肌动蛋白的黏附结构称为内侧足或足体，被认为在降解细胞外基质方面起着关键作用。我已经研究了在Src转化的NIH3T3细胞中内多糖/足体形成的机制。在本研究中，基于RNAi的结果、结合蛋白的质谱学鉴定、蛋白质相互作用和活细胞成像分析，我建立了一个关于印迹草形成的逐步机制。由于蛋白质的磷酸化状态和质膜上的磷脂酰肌醇组成的变化，内陷足起源于局灶性粘连(FAs)。肌动蛋白聚合的开始是由PI(3，4)P2的产生和Tks5的募集以及N-WASP的积累触发的。这一步骤涉及在FA中Tks5与PI(3，4)P2和Grb2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