MICA: Control of tumour cell apoptosis by nuclear F-actin bundling

大量的临床研究已经确定了一种名为fascin的蛋白质，它在一系列人类癌症中以极高的水平存在。关于这种蛋白质是如何控制的知之甚少，但我们知道，降低我们在实验室中培养的癌细胞的水平会降低这些细胞进行转移扩散的能力。Fascin是一个令人兴奋的治疗转移的潜在靶点，但在我们更多地了解它是如何控制的之前，我们无法设计针对其功能的药物。该项目旨在研究控制细胞中肌成束蛋白功能的因素，并确定蛋白质如何响应癌细胞周围环境的变化。目前知识的主要差距之一是对调节癌症进展和转移的因素的详细理解。该项目将有助于识别可导致癌细胞侵袭增加的新蛋白质，从而为设计未来的治疗方法提供新的可能靶点。我们将研究蛋白质的结构，并确定该分子中对控制细胞中不同功能至关重要的特定位置和区域。然后，我们将分离与这些形式的肌成束蛋白结合的蛋白质，并描述这种结合是如何发生的。然后，我们将在实验室中使用人类癌细胞来研究这些新发现的负责促进肌成束蛋白功能的蛋白质，并确定它们是如何被控制的。最后，我们将使用不同的策略来抑制这些相关蛋白，并确定它们如何控制可能导致促进转移性疾病的癌细胞行为。最终，这项研究可能会导致确定新药物和治疗剂的设计和开发的目标，以防止癌症的生长和扩散。

A large number of clinical studies have identified a protein called fascin that is present at extremely high levels in a range of human cancers. Very little is known about how this protein is controlled, but we know that reducing levels in cancer cells that we grow in the lab results in reducing the ability of those cells to undergo metastatic spread. Fascin is an exciting potential target to treat metastasis, but until we know more about how it is controlled, we cannot design drugs to target its function. This project aims to study the factors that control fascin function in cells and identify how the protein responds to changes in the environment that surrounds cancer cells. One of the major gaps in current knowledge is a detailed understanding of the factors regulating cancer progression and metastasis. This project will help to identify new proteins that can lead to increased cancer cell invasion and therefore provide new possible targets for designing future treatments. We will study the structure of the protein and identify specific the places and regions within this molecule that are important for controlling different functions in cells. We will then isolate proteins that bind to these forms of fascin and characterize how this binding occurs. We will then use human cancer cells in the lab to study these newly identified proteins that are responsible for promoting the fascin function and determine how they are controlled. Finally, we will use different strategies to inhibit these associated proteins and determine how they control cancer cell behavior that may lead to promotion of metastatic disease. Ultimately this study could lead to the identification of targets for the design and development of new drugs and therapeutic agents to prevent cancer growth and spread.