Mechanisms of Dok2 signaling during TGF beta-induced EMT

TGFβ 诱导 EMT 过程中 Dok2 信号传导机制

• 批准号: 92177455
• 负责人: Dr. Elena Zimina
• 金额: --
• 依托单位: Faculty of Dentistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/92177455?language=en
• 关键词: Mechanisms; Dok2; signaling; during; TGF

Epithelial-mesenchymal transition (EMT) normally occurs during embryonic morphogenesis, but it is also involved in the progression of primary tumors towards metastases. EMT is a process of disaggregation of the structured epithelial units to enable cell movement and morphogenesis. EMT involves the remodeling of cell-extracellular matrix (ECM) interactions. Recent advances have provided a more detailed understanding of the molecular mechanisms governing EMT in tumor progression and have underlined the key mediating role of TGF beta (TGFβ) in this process. The laboratory of Dr. Attisano recently identified the adaptor protein Dok2, a member of Dok-protein family, to be essential for TGFβ−induced ΕΜΤ. Observations by Dr. Attisano s laboratory suggest an important role for Dok2 in the reorganization of cell- ECM interactions. The intended research aims to examine the molecular mechanisms whereby Dok2 functions in TGFβ−induced EMT. We plan to determine how Dok2 influences cell-ECM adhesion and associated signaling upon TGFβ−dependent EMT. Understanding of Dok2 function upon TGFβ− induced EMT is especially relevant for cancer cell invasion and metastasis.

上皮-间质转化（EMT）通常发生在胚胎形态发生期间，但它也参与原发性肿瘤向转移的进展。EMT是结构化上皮单位的分解过程，以实现细胞运动和形态发生。EMT涉及细胞-细胞外基质（ECM）相互作用的重塑。最近的进展提供了对肿瘤进展中EMT的分子机制的更详细的理解，并强调了TGF β（TGFβ）在此过程中的关键介导作用。Attisano博士的实验室最近鉴定了Dok蛋白家族成员Dok 2的衔接蛋白，它是TGFβ-诱导的EMT所必需的。Attisano博士实验室的观察表明，Dok 2在细胞- ECM相互作用的重组中起着重要作用。该研究旨在研究Dok 2在TGFβ−诱导的EMT中发挥作用的分子机制。我们计划确定Dok 2如何影响细胞-ECM粘附和TGFβ依赖性EMT的相关信号传导。了解Dok 2在TGFβ−诱导的EMT中的功能与癌细胞侵袭和转移特别相关。