The regulation of hybrid-EMT and metastasis in colorectal cancer

结直肠癌是英国癌症相关死亡的最常见原因之一，转移（癌细胞扩散到远处器官）是主要原因。对于扩散的癌症来说，肿瘤细胞需要侵入局部组织，脱离原发肿瘤，然后在继发部位重新定居。人们认为，一种称为上皮向间充质转化（EMT）的过程对癌症扩散很重要，但对其如何控制却知之甚少。这种知识的缺乏影响了我们开发新疗法的能力，这些新疗法可能会抑制EMT并为患者提供益处。本研究的目的是试图了解EMT过程是如何启动的，特别是肿瘤细胞如何维持在被认为对转移很重要的中间状态。我们的目标是详细研究我们认为控制这一过程的基因的功能，并发现它们是否对转移很重要。我们还旨在直接测试这一过程是否存在于侵袭性人类癌症中，以及它是否有助于预测患者的预后。重要的是，我们还将尝试识别驱动转移的候选分子，这些分子可以被治疗药物抑制。总之，这项研究将导致增加对结直肠癌如何传播的理解。这可能会导致如何管理这种疾病的最具侵略性的形式的重要进展，并最终导致新的治疗方法。此外，由于肿瘤转移是许多其他癌症类型死亡的主要原因，因此它也可能对其他癌症的治疗产生深远的影响。

Colorectal cancer is one of the commonest causes of cancer related death in the UK with metastasis (the spread of cancer cells to distant organs) the primary cause. For cancers to spread tumour cells need to invade into local tissues, break away from the primary tumour and then resettle at secondary sites. A process called epithelial to mesenchymal transition (EMT) is believed to be important for cancer spread but how it is controlled is poorly understood. This lack of knowledge impacts on our ability to develop new therapies that might inhibit it and provide benefit to patients.The purpose of this research is to try to understand how the EMT process is initiated and in particular how tumour cells are maintained in an intermediate state thought to be important for metastasis. We aim to investigate in detail the function of the genes we have identified that we think control this process and discover whether they are important for metastasis. We also aim to directly test if this process is found in aggressive human cancers and whether it can help predict patient outcome. Importantly, we will also attempt to identify candidate molecules that drive metastasis that could be inhibited by therapeutic drugs. Together, this research will lead to increased understanding of how colorectal cancer spreads. This could lead to important advances in how to manage the most aggressive forms of this disease and ultimately lead to new therapies for its treatment. Furthermore, since tumour metastasis is the primary cause of death in many other cancer types it could have far reaching implications for the treatment of other cancers as well.