Mechanisms of Dok2 signaling during TGF beta-induced EMT

上皮-间质转化（Epithelial-mesenchymal transition， EMT）通常发生在胚胎形态发生过程中，但它也参与原发肿瘤向转移的进展。EMT是一个结构化上皮单位分解的过程，使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。最近的进展为肿瘤进展中EMT的分子机制提供了更详细的了解，并强调了TGFβ在这一过程中的关键介导作用。Attisano博士的实验室最近发现了衔接蛋白Dok2，它是dok蛋白家族的一员，对TGFβ诱导ΕΜΤ至关重要。Attisano博士实验室的观察结果表明，Dok2在细胞- ECM相互作用的重组中起着重要作用。本研究旨在研究Dok2在TGFβ−诱导的EMT中发挥作用的分子机制。我们计划确定Dok2如何影响TGFβ依赖性EMT的细胞- ecm粘附和相关信号。了解Dok2在TGFβ−诱导的EMT中的功能与癌细胞的侵袭和转移特别相关。

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.