C-Met internalisation and tumour cell migration

C-Met 内化和肿瘤细胞迁移

• 批准号: G0501003/1
• 负责人: Stephanie Kermorgant
• 金额: $ 41.28万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501003%2F1
• 关键词: Met; internalisation; tumour; cell; migration

Approximately 160,000 people die from cancer every year in the UK alone. Most cancers start as a small lump of abnormal cells (a tumour). As the tumour grows, some cancer cells can detach from the tumour, move away and eventually colonise some healthy part of the body. This aggressive process is called metastasis and is the major cause of treatment failure and the principal cause of death in human cancer. My research focuses on understanding the role of a molecule called c-Met in human cancer metastasis. C-Met is present at the surface of the cells and is activated by binding to its ligand the Hepatocyte Growth Factor (HGF). I want to understand how the activated c-Met transmits signals inside the cancer cell to tell it to move away from the primary tumour. Hopefully this will allow us to design drugs to stop this process. My project is based on the novel concept, for which I already had found evidence, is that surface receptors have to enter into the cell for their correct function and subsequent cell responses. In this project, by using established biochemical approaches, I will block the entry of c-Met into the cancer cell and analyse the consequences of this block on tumour cell movement in vitro and in experimental animals. Using biochemical and biological approaches, including state of the art microscopy, I will follow the movement of c-Met and the generation of signals inside the cell to understand these mechanisms at the molecular level. I will then design ways to inhibit these molecular events in the cell to block cell movement and tumour spread.

仅在英国，每年就有大约16万人死于癌症。大多数癌症开始于一小块异常细胞（肿瘤）。随着肿瘤的生长，一些癌细胞可以从肿瘤中分离出来，离开并最终定居在身体的一些健康部位。这种侵袭性过程称为转移，是治疗失败的主要原因，也是人类癌症死亡的主要原因。我的研究重点是了解一种名为c-Met的分子在人类癌症转移中的作用。C-Met存在于细胞表面，并通过与其配体肝细胞生长因子（HGF）结合而被激活。我想了解激活的c-Met如何在癌细胞内传递信号，告诉它远离原发性肿瘤。希望这将使我们能够设计药物来阻止这一过程。我的项目是基于一个新的概念，我已经找到了证据，那就是表面受体必须进入细胞才能发挥正确的功能和随后的细胞反应。在这个项目中，通过使用已建立的生物化学方法，我将阻止c-Met进入癌细胞，并分析这种阻断对体外和实验动物肿瘤细胞运动的影响。使用生物化学和生物学方法，包括最先进的显微镜，我将跟踪c-Met的运动和细胞内信号的产生，以在分子水平上了解这些机制。然后，我将设计方法来抑制细胞中的这些分子事件，以阻止细胞运动和肿瘤扩散。