Urokinase Receptor-initiated Cell-signaling

尿激酶受体启动的细胞信号传导

基本信息

  • 批准号:
    7909207
  • 负责人:
  • 金额:
    $ 27.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-08-01 至 2011-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This research project focuses on the urokinase receptor (uPAR), a multifunctional GPI-anchored membrane protein that has been implicated in breast cancer progression. Our long-term goal is to understand mechanisms by which uPAR regulates cancer cell physiology. uPAR binds at least two ligands: the plasminogen activator, urokinase-type plasminogen activator (uPA), and the provisional extracellular matrix protein, vitronectin. Within the plasma membrane, uPAR laterally associates with integrins, G-protein coupled receptors, and receptor-tyrosine kinases (RTKs). These "co-receptor" interactions result in the formation of a dynamic, multiprotein signaling receptor complex (MSRC). uPA and vitronectin activate uPAR-dependent cell signaling; however, the pathways are distinct. uPA-binding activates ERK/MAP kinase whereas vitronectin activates Rad. Other signaling proteins, such as STAT-5b, may be recruited downstream of uPAR depending on the co-receptors that associate with uPAR in the MSRC. Co-receptors also determine the nature of the cellular response, such as whether uPA is mitogenic. In this application, four specific aims are proposed. In Aim 1, we propose to elucidate the pathway that leads from uPAR to Rac1 and determine the mechanism by which ligation of a single receptor (uPAR) with two distinct ligands (uPA or vitronectin) causes completely distinct cell signaling responses. Aim 2 builds on preliminary data in which we have demonstrated that uPAR over-expression induces epithelial-mesenchymal transformation (EMT), a well known process associated with cancer progression in which epithelial cells adopt a fibroblast-like morphology, lose cell-cell contacts, demonstrate increased vimentin expression and decreased E-cadherin expression. Experiments planned in Aim 2 will determine the mechanism by which uPAR induces EMT. In Aim 3, we will test the hypothesis that uPAR-dependent cell signaling regulates the response of cancer cells not only to uPA but also to growth factors such as EGF and PDGF. Understanding crosstalk between uPAR and RTKs is a critical objective. Finally, in Aim 4, we propose studies to determine whether uPAR-dependent cell signaling is involved in cancer development and progression in vivo. Xenograft and spontaneous neoplasia mouse-model systems will be applied. These studies will elucidate the role of uPAR in cancer and provide critical information regarding how uPAR may be targeted for novel cancer therapeutics design.
描述(由申请人提供):本研究项目的重点是尿激酶受体(uPAR),一种多功能GPI锚定膜蛋白,与乳腺癌进展有关。我们的长期目标是了解uPAR调节癌细胞生理学的机制。uPAR结合至少两种配体:纤溶酶原激活物,尿激酶型纤溶酶原激活物(uPA),和临时细胞外基质蛋白,玻连蛋白。在质膜内,uPAR与整合素、G蛋白偶联受体和受体酪氨酸激酶(RTK)横向缔合。这些“共受体”相互作用导致形成动态的多蛋白信号受体复合物(MSRC)。uPA和玻连蛋白激活uPAR依赖的细胞信号传导;然而,途径是不同的。uPA结合激活ERK/MAP激酶,而玻连蛋白激活Rad。其他信号传导蛋白,如STAT-5 b,可能被募集到uPAR的下游,这取决于与MSRC中uPAR相关的共受体。辅助受体还决定细胞反应的性质,例如uPA是否是促有丝分裂的。在本申请中,提出了四个具体目标。在目标1中,我们提议阐明从uPAR到Rac 1的途径,并确定单个受体(uPAR)与两种不同配体(uPA或玻连蛋白)的连接引起完全不同的细胞信号传导反应的机制。目的2建立在初步数据的基础上,我们已经证明uPAR过表达诱导上皮-间质转化(EMT),这是一种与癌症进展相关的众所周知的过程,其中上皮细胞采用成纤维细胞样形态,失去细胞-细胞接触,表现出波形蛋白表达增加和E-钙粘蛋白表达减少。目标2中计划的实验将确定uPAR诱导EMT的机制。在目标3中,我们将检验uPAR依赖性细胞信号传导不仅调节癌细胞对uPA的反应,而且调节癌细胞对生长因子如EGF和PDGF的反应的假设。了解uPAR和RTK之间的串扰是一个关键目标。最后,在目标4中,我们提出研究以确定uPAR依赖性细胞信号传导是否参与体内癌症的发展和进展。将应用异种移植和自发性肿瘤小鼠模型系统。这些研究将阐明uPAR在癌症中的作用,并提供有关uPAR如何成为新型癌症治疗设计靶点的关键信息。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

STEVEN L. GONIAS其他文献

STEVEN L. GONIAS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('STEVEN L. GONIAS', 18)}}的其他基金

A novel role for Reelin therapeutics in inflammatory bowel disease
Reelin 疗法在炎症性肠病中的新作用
  • 批准号:
    10079713
  • 财政年份:
    2020
  • 资助金额:
    $ 27.35万
  • 项目类别:
Regulation of Inflammation by the Fibrinolytic System
纤溶系统对炎症的调节
  • 批准号:
    10358335
  • 财政年份:
    2017
  • 资助金额:
    $ 27.35万
  • 项目类别:
Regulation of Inflammation by the Fibrinolytic System
纤溶系统对炎症的调节
  • 批准号:
    9913997
  • 财政年份:
    2017
  • 资助金额:
    $ 27.35万
  • 项目类别:
Regulation of Inflammation by the Fibrinolytic System
纤溶系统对炎症的调节
  • 批准号:
    10557130
  • 财政年份:
    2017
  • 资助金额:
    $ 27.35万
  • 项目类别:
Regulation of Inflammation by the Fibrinolytic System
纤溶系统对炎症的调节
  • 批准号:
    9285496
  • 财政年份:
    2017
  • 资助金额:
    $ 27.35万
  • 项目类别:
Regulation of Inflammation by the Fibrinolytic System
纤溶系统对炎症的调节
  • 批准号:
    10693590
  • 财政年份:
    2017
  • 资助金额:
    $ 27.35万
  • 项目类别:
Targeting the Urokinase Receptor in Glioblastoma Multiforme
靶向多形性胶质母细胞瘤中的尿激酶受体
  • 批准号:
    8613477
  • 财政年份:
    2013
  • 资助金额:
    $ 27.35万
  • 项目类别:
Targeting the Urokinase Receptor in Glioblastoma Multiforme
靶向多形性胶质母细胞瘤中的尿激酶受体
  • 批准号:
    8501950
  • 财政年份:
    2013
  • 资助金额:
    $ 27.35万
  • 项目类别:
Targeting the Urokinase Receptor in Glioblastoma Multiforme
靶向多形性胶质母细胞瘤中的尿激酶受体
  • 批准号:
    9023503
  • 财政年份:
    2013
  • 资助金额:
    $ 27.35万
  • 项目类别:
Targeting the Urokinase Receptor in Glioblastoma Multiforme
靶向多形性胶质母细胞瘤中的尿激酶受体
  • 批准号:
    9215655
  • 财政年份:
    2013
  • 资助金额:
    $ 27.35万
  • 项目类别:

相似海外基金

How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
  • 批准号:
    2315783
  • 财政年份:
    2023
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
  • 批准号:
    2719534
  • 财政年份:
    2022
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633211
  • 财政年份:
    2020
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
  • 批准号:
    20K01113
  • 财政年份:
    2020
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2436895
  • 财政年份:
    2020
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633207
  • 财政年份:
    2020
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
  • 批准号:
    426559561
  • 财政年份:
    2019
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
  • 批准号:
    2236701
  • 财政年份:
    2019
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
  • 批准号:
    19K01745
  • 财政年份:
    2019
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
  • 批准号:
    415543446
  • 财政年份:
    2019
  • 资助金额:
    $ 27.35万
  • 项目类别:
    Research Fellowships
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了