RAB11 RECYCLING IN OVARIAN CANCER METASTASIS

卵巢癌是英国女性中第六常见的癌症，大多数女性被诊断患有一种称为高级别浆液性卵巢癌（HGSOC）的特别具有侵袭性和致命性的癌症。近年来，HGSOC患者的不良前景几乎没有改变，并且很少有靶向治疗方法被发现。我们的研究重点是细胞表面蛋白的定位如何通过内吞运输控制，从细胞表面去除的货物被运送回来执行其功能。Rab11是与卵巢癌相关的内吞运输的主要调节因子，我们将把注意力集中在这个蛋白质家族上。我们将研究HGSOC细胞如何使用内吞运输来控制它们与周围环境的相互作用，研究参与递送货物的机制，并确定控制HGSOC细胞如何在癌症扩散时侵入并在新部位增殖的新货物。由于该项目是与科学家和临床医生的密切合作，我们可以获得HGSOC患者样本以及分离患者细胞和组织的知识，以便在人类中研究该疾病。我们将努力使用来自同一患者的细胞和组织，以了解卵巢癌扩散的过程。我们还将在化疗前后从患者身上采集细胞和组织，以便我们能够了解Rab11驱动的内吞运输如何帮助HGSOC细胞存活并避免化疗。这将使我们能够深入了解卵巢癌患者的新的潜在疗法。

Ovarian cancer is the 6th most common cancer in women in the UK, and most women are diagnosed with a particularly aggressive and lethal form called high grade serous ovarian cancer (HGSOC). The poor outlook for HGSOC patients has changed very little over recent years, and few targeted therapies have been discovered.Our study focuses on how the positioning of cell surface proteins is controlled by endocytic trafficking, where cargoes removed from the cell surface are delivered back to perform their function. Rab11 is a major regulator of endocytic trafficking that is linked to ovarian cancers, and we will focus our attention on this family of proteins. We will investigate how HGSOC cells use endocytic trafficking to control their interaction with the surrounding environment, study the machinery involved in delivering cargoes and identify new cargoes that control how HGSOC cells invade into and proliferate at new sites as the cancer spreads. Because this project is a close collaboration with scientists and clinicians, we have access to HGSOC patient samples and the knowledge to isolate patient cells and tissues in order to study the disease in humans. We will work towards using cells and tissues from the same patient, in order to understand the process of ovarian cancer spread. We will also take cells and tissue from patients before and after chemotherapy, so that we can understand how Rab11 driven endocytic trafficking can also help HGSOC cells to survive and avoid chemotherapy. This will allow us to gain insight into new potential therapies for ovarian cancer patients.