RAB11 RECYCLING IN OVARIAN CANCER METASTASIS

卵巢癌是英国女性中第六大最常见的癌症，大多数女性被诊断出患有一种特别具有侵略性和致命性的高级别浆液性卵巢癌（HGSOC）。近年来，HGSOC患者的不良前景几乎没有改变，并且很少发现靶向治疗方法。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，在内吞运输中，从细胞表面移除的货物被运送回来执行它们的功能。Rab11是与卵巢癌相关的内噬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，研究运送货物所涉及的机制，并确定新的货物，控制HGSOC细胞如何入侵并在癌症扩散时在新的位点增殖。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，以了解卵巢癌的扩散过程。我们还将从化疗前后的患者身上提取细胞和组织，从而了解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.