RAB11 RECYCLING IN OVARIAN CANCER METASTASIS

卵巢癌是英国女性第六常见的癌症，大多数女性被诊断出患有一种特别侵袭性和致命性的形式，称为高级别浆液性卵巢癌(HGSOC)。近年来，HGSOC患者的糟糕前景几乎没有改变，也几乎没有发现有针对性的治疗方法。我们的研究重点是细胞表面蛋白的定位是如何通过内吞运输来控制的，即从细胞表面移除的货物被送回履行其功能。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家族上。我们将研究HGSOC细胞如何利用内吞运输来控制它们与周围环境的相互作用，研究运输货物的机制，并确定控制HGSOC细胞如何在癌症扩散时侵入和在新部位增殖的新货物。由于这个项目是与科学家和临床医生的密切合作，我们可以获得HGSOC患者样本和分离患者细胞和组织的知识，以便研究人类疾病。我们将致力于使用同一患者的细胞和组织，以了解卵巢癌的扩散过程。我们还将从化疗前和化疗后的患者身上提取细胞和组织，以便我们能够了解Rab11驱动的内吞运输如何也可以帮助HGSOC细胞存活并避免化疗。这将使我们能够洞察卵巢癌患者的新的潜在治疗方法。

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.