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The role of RNA Binding Proteins (RBPs) in breast cancer progression and metastasis

RNA 结合蛋白 (RBP) 在乳腺癌进展和转移中的作用

基本信息

批准号：
MR/P009417/1
负责人：
Faraz Mardakheh
金额：
$ 155.3万
依托单位：
Queen Mary University of London
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FP009417%2F1
关键词：
role RNA Binding Proteins RBPs

项目摘要

Metastasis is the process by which cancer spreads through the body and colonises distant, sometimes vital, organs and tissues. It is estimated that more than 90% of all cancer related mortalities are due to metastasis. In breast cancer in particular, despite great advances in detection and treatment of the disease over the past decades, related mortality rates have remained high due to recurrence of cancer as metastases in secondary organs and tissues, which often happens several years after the initial diagnosis and treatment. Importantly, no therapies are currently available for breast cancer patients to prevent the spread of cancer within the body.To metastasise, cancer cells must acquire the capacity to invade into their surroundings, move through tissues and vasculature, and colonise distant sites in the body. This requires activation of cellular pathways that promote cell movement. While much has been revealed on molecular machineries that mediate cell movement, little is known about regulators of movement which become abhorrently activated during metastasis. Recent works by me and other have revealed that an unexpected group of cellular proteins, called RNA Binding Proteins (RBPs), can promote cancer cell movement and invasion, ultimately leading to metastasis. However, it is unclear how different RBPs function to promote the movement of cancer cells, and more importantly, whether they could be targeted to tackle metastasis.My research aims to reveal which RBPs are involved in regulating different aspects of cancer cell movement, cancer invasion, and ultimately metastasis in breast cancer. I will use cutting edge methodologies that I have been developing and using during my previous work, to systematically assess which RBPs are linked to the movement and metastasis of breast cancer cells. I will then assess how these RBPs are promoting movement and metastasis at the molecular level. Ultimately, such molecular level understanding of the processes that control cancer cell movement and metastasis may be useful for designing novel drugs to intervene in the metastatic process.

转移是指癌症在体内扩散，并在远处（有时是重要的）器官和组织中定居的过程。据估计，90%以上的癌症相关死亡是由转移引起的。特别是在乳腺癌方面，尽管过去几十年来在该疾病的检测和治疗方面取得了很大进展，但由于癌症在次要器官和组织中转移而复发，相关死亡率仍然很高，这种情况往往发生在最初诊断和治疗的几年后。重要的是，目前还没有针对乳腺癌患者的治疗方法来防止癌症在体内扩散。为了转移，癌细胞必须获得侵入周围环境的能力，通过组织和血管系统移动，并在身体的远处定居。这需要激活促进细胞运动的细胞通路。虽然已经揭示了许多介导细胞运动的分子机制，但对于在转移过程中被令人厌恶地激活的运动调节因子知之甚少。我和其他人最近的工作揭示了一组意想不到的细胞蛋白，称为RNA结合蛋白（rbp），可以促进癌细胞的运动和侵袭，最终导致转移。然而，目前尚不清楚不同的rbp如何促进癌细胞的运动，更重要的是，它们是否可以靶向治疗转移。我的研究旨在揭示哪些rbp参与调节乳腺癌中癌细胞运动、癌症侵袭和最终转移的不同方面。我将使用我在以前的工作中开发和使用的尖端方法，系统地评估哪些rbp与乳腺癌细胞的运动和转移有关。然后，我将评估这些rbp如何在分子水平上促进运动和转移。最终，这种对控制癌细胞运动和转移过程的分子水平的理解可能有助于设计新的药物来干预转移过程。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An ERK1/2-driven RNA-binding switch in nucleolin drives ribosome biogenesis and pancreatic tumorigenesis downstream of RAS oncogene.

DOI：
10.15252/embj.2022110902
发表时间：
2023-06-01
期刊：
EMBO JOURNAL
影响因子：
11.4
作者：
Azman, Muhammad S.;Alard, Emilie L.;Dodel, Martin;Capraro, Federica;Faraway, Rupert;Dermit, Maria;Fan, Wanling;Chakraborty, Alina;Ule, Jernej;Mardakheh, Faraz K.
通讯作者：
Mardakheh, Faraz K.

ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning.

DOI：
10.1242/dev.200528
发表时间：
2022-07-01
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
通讯作者：

Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells.

DOI：
10.1016/j.devcel.2020.10.006
发表时间：
2020-11-09
期刊：
Developmental cell
影响因子：
11.8
作者：
Dermit M;Dodel M;Lee FCY;Azman MS;Schwenzer H;Jones JL;Blagden SP;Ule J;Mardakheh FK
通讯作者：
Mardakheh FK

Purification and quantitative proteomic analysis of cell bodies and protrusions.