Rap 1-Mediated Protein Transport in Oral Cancer

Rap 1 介导的口腔癌蛋白质转运

基本信息

  • 批准号:
    7082134
  • 负责人:
  • 金额:
    $ 7.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-08-01 至 2007-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The aggressive surgical and radiologic treatment for oral cancer is physically and emotionally debilitating and has not improved prognosis (<50% 5 year survival) in the past four decades. Since cancer is the endpoint of uncontrolled cell proliferation, elucidation of the signaling cascade controlling cell proliferation in normal and malignant oral keratinocytes is critical to the identification of specific treatment targets. In oral cancer these signaling mechanisms are relatively uncharacterized but an exciting and significant area of research is the signaling cascade triggered by rap1A and rap1B, ras-like proteins that have been shown to have oncogenic and/or tumor suppressive properties in mesenchymal cells. In previous studies we found that inactivation of rap1 by rap1GAP, stimulated proliferation in non-malignant keratinocytes but inhibited proliferation in oral cancer. Rap1GAP inactivates rap1A and rap1B, the 95% identical isoforms, both of which are expressed in normal and malignant keratinocytes. Although rap1A and rap1B have been linked to growth in several cells, the interaction between these proteins in the same cell has not been explored. Furthermore, our laboratory recently discovered that rap1 is strongly expressed in the nucleus of malignant keratinocytes and that growth factors in serum induce nuclear translocation. Hence, it is likely that rap1A and rap1B interact with transport and effector proteins to regulate proliferation. The central hypothesis is that in oral cancer there is a disruption in rap1-mediated nuclear transport with enhanced nuclear translocation of pro-proliferative proteins. The objectives of this proposal are to investigate the interaction between rap1A and rap1B in regulating proliferation in normal and malignant keratinocytes; and to identify the proteins that are transported by rap1A and rap1B to the nucleus to regulate proliferation. The significance of this research is that it explores an important and novel mechanism for nucleocytoplasmic transport of pro-proliferative proteins in oral cancer, thereby identifying novel treatment targets.
描述(由申请人提供):在过去的40年里,口腔癌的积极手术和放射治疗使身体和情感都变得虚弱,并且没有改善预后(50%的5年生存率)。由于癌症是不受控制的细胞增殖的终点,阐明正常和恶性口腔角质形成细胞中控制细胞增殖的信号级联对于确定特定的治疗靶点至关重要。在口腔癌中,这些信号机制相对较少,但一个令人兴奋和有意义的研究领域是由Rap1A和Rap1B触发的信号级联反应,这是一种已被证明在间充质细胞中具有致癌和/或肿瘤抑制特性的ras样蛋白。在以前的研究中,我们发现Rap1GAP使Rap1失活,促进了非恶性角质形成细胞的增殖,但抑制了口腔癌的增殖。Rap1GAP使Rap1A和Rap1B失活,这两种95%相同的亚型在正常和恶性角质形成细胞中都有表达。虽然Rap1A和Rap1B在几个细胞中与生长有关,但在同一细胞中这些蛋白质之间的相互作用还没有被探索过。此外,我们的实验室最近发现,RAP1在恶性角质形成细胞的细胞核中强烈表达,并且血清中的生长因子可以诱导核转位。因此,Rap1A和Rap1B很可能与运输和效应蛋白相互作用来调节增殖。中心假说是,在口腔癌中,随着促增殖蛋白的核转位增强,RAP1介导的核运输受到干扰。本研究的目的是探讨在正常角质形成细胞和恶性角质形成细胞中,Rap1A和Rap1B在调控细胞增殖中的相互作用,并确定由Rap1A和Rap1B转运到细胞核以调节增殖的蛋白质。这项研究的意义在于,它探索了口腔癌中促增殖蛋白的核浆转运的重要和新的机制,从而确定了新的治疗靶点。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma.
  • DOI:
    10.1038/onc.2011.141
  • 发表时间:
    2011-10-20
  • 期刊:
  • 影响因子:
    8
  • 作者:
    Banerjee, R.;Mani, R-S;Russo, N.;Scanlon, C. S.;Tsodikov, A.;Jing, X.;Cao, Q.;Palanisamy, N.;Metwally, T.;Inglehart, R. C.;Tomlins, S.;Bradford, C.;Carey, T.;Wolf, G.;Kalyana-Sundaram, S.;Chinnaiyan, A. M.;Varambally, S.;D'Silva, N. J.
  • 通讯作者:
    D'Silva, N. J.
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Nisha J D'Silva其他文献

Nisha J D'Silva的其他文献

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{{ truncateString('Nisha J D'Silva', 18)}}的其他基金

Downstream effects of HPV integration on survival/metastasis in oropharyngeal cancer
HPV 整合对口咽癌生存/转移的下游影响
  • 批准号:
    10660945
  • 财政年份:
    2020
  • 资助金额:
    $ 7.42万
  • 项目类别:
Downstream effects of HPV integration on survival/metastasis in oropharyngeal cancer
HPV 整合对口咽癌生存/转移的下游影响
  • 批准号:
    10204988
  • 财政年份:
    2020
  • 资助金额:
    $ 7.42万
  • 项目类别:
Downstream effects of HPV integration on survival/metastasis in oropharyngeal cancer
HPV 整合对口咽癌生存/转移的下游影响
  • 批准号:
    10066438
  • 财政年份:
    2020
  • 资助金额:
    $ 7.42万
  • 项目类别:
Downstream effects of HPV integration on survival/metastasis in oropharyngeal cancer
HPV 整合对口咽癌生存/转移的下游影响
  • 批准号:
    10438782
  • 财政年份:
    2020
  • 资助金额:
    $ 7.42万
  • 项目类别:
Improving Survival in Oral Cancer by Disruption of Tumor Progression
通过破坏肿瘤进展来提高口腔癌的生存率
  • 批准号:
    10405550
  • 财政年份:
    2017
  • 资助金额:
    $ 7.42万
  • 项目类别:
Improving Survival in Oral Cancer by Disruption of Tumor Progression
通过破坏肿瘤进展来提高口腔癌的生存率
  • 批准号:
    10631930
  • 财政年份:
    2017
  • 资助金额:
    $ 7.42万
  • 项目类别:
Impact of nerves on cancer initiating cells and tumor progression
神经对癌症起始细胞和肿瘤进展的影响
  • 批准号:
    8871714
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Impact of nerves on cancer initiating cells and tumor progression
神经对癌症起始细胞和肿瘤进展的影响
  • 批准号:
    8722135
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Role of EZH2 in Invasion and Migration in the Oral Mucosa
EZH2 在口腔粘膜侵袭和迁移中的作用
  • 批准号:
    8743202
  • 财政年份:
    2013
  • 资助金额:
    $ 7.42万
  • 项目类别:
Role of EZH2 in Invasion and Migration in the Oral Mucosa
EZH2 在口腔粘膜侵袭和迁移中的作用
  • 批准号:
    8576552
  • 财政年份:
    2013
  • 资助金额:
    $ 7.42万
  • 项目类别:

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内在无序蛋白 NPM1 调节细胞生长的新机制
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