Molecular Mechanism and Therapy for Ocular Melanoma
眼部黑色素瘤的分子机制及治疗
基本信息
- 批准号:9328539
- 负责人:
- 金额:$ 48.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-14 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAnimal ModelCRISPR/Cas technologyCell Culture TechniquesCell LineCell physiologyCellsCessation of lifeCommon NeoplasmCutaneous MelanomaDNA Sequence AlterationEyeEye NeoplasmsGNAQ geneGenesGeneticGoalsLuciferasesMalignant NeoplasmsMelanoma CellMetastatic Neoplasm to the LiverModelingMolecularMutateMutationNatureNeoplasm MetastasisOcular MelanomaOncoproteinsPathway interactionsPhosphorylationPlayProteinsRecurrenceRoleSpecificityTechniquesTestingTherapeuticTherapeutic InterventionTumor Suppressor ProteinsUveal MelanomaVerteporfincancer geneticscancer genomicsexperimental studygene interactiongenetic analysisinhibitor/antagonistinsightkillingsmouse modelmutantoutcome forecastrepairedtherapeutic targettooltumor growthtumorigenesis
项目摘要
Abstract
Uveal melanoma is the most common ocular tumor in adults. It harbors genetic mutations very different
from those seen in cutaneous melanoma. Liver metastasis is common in uveal melanoma and contributes to the
very poor prognosis with average survival of several months. Currently there is no treatment for metastatic uveal
melanoma. Activating mutations in GNAQ and GNA11 are the most important cancer drivers, as approximately
80% of uveal melanomas have mutations in either GNAQ or GNA11. Our recent studies have shown that the
mutant GNAQ/11 potently activates the YAP oncoprotein, which is a key component of the Hippo tumor
suppressor pathway. Moreover, the elevated YAP activity is essential for tumor growth of uveal melanoma cells
containing an activating mutation in GNAQ/11. Besides GNAQ/11, mutations in BAP1, SF3B1, and EIF1AX are
also frequently observed in uveal melanoma in a mutually exclusive manner. However, a mechanistic
understanding of these genes in uveal melanoma and their functional interactions are largely unknown. The
major goals of this project are to determine the contributions of the genes commonly mutated in uveal melanoma
and their functional interaction in promoting tumorigenesis of uveal melanoma. We also aim to characterize and
validate potential therapeutic targets and tools for treatment of uveal melanoma.
摘要
葡萄膜黑色素瘤是成人最常见的眼部肿瘤。它所携带的基因突变
与皮肤黑色素瘤中所见不同。肝转移在葡萄膜黑色素瘤中是常见的,并有助于葡萄膜黑色素瘤的发生。
预后极差,平均存活数个月。目前还没有治疗转移性葡萄膜炎的方法
黑素瘤GNAQ和GNA 11中的激活突变是最重要的癌症驱动因素,大约
80%的葡萄膜黑色素瘤在GNAQ或GNA 11中存在突变。我们最近的研究表明,
突变体GNAQ/11有效激活雅普癌蛋白,这是Hippo肿瘤的关键成分
抑制子途径此外,升高的雅普活性对于葡萄膜黑色素瘤细胞的肿瘤生长是必需的
在GNAQ/11中含有激活突变。除GNAQ/11外,BAP 1、SF 3B 1和EIF 1AX的突变也是一个重要的基因突变。
在葡萄膜黑色素瘤中也经常以相互排斥的方式观察到。然而,一个机械的
对葡萄膜黑色素瘤中这些基因及其功能相互作用的了解在很大程度上是未知的。的
这个项目的主要目标是确定葡萄膜黑色素瘤中常见的突变基因的作用
以及它们在促进葡萄膜黑色素瘤发生中的功能相互作用。我们还旨在描述和
验证用于治疗葡萄膜黑色素瘤的潜在治疗靶点和工具。
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)
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Kun-Liang Guan其他文献
Kun-Liang Guan的其他文献
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{{ truncateString('Kun-Liang Guan', 18)}}的其他基金
Functional interplay between Hippo and estrogen receptor ESR1
Hippo 和雌激素受体 ESR1 之间的功能相互作用
- 批准号:
10339901 - 财政年份:2022
- 资助金额:
$ 48.8万 - 项目类别:
Molecular Mechanism and Therapy for Ocular Melanoma
眼部黑色素瘤的分子机制及治疗
- 批准号:
9453662 - 财政年份:2017
- 资助金额:
$ 48.8万 - 项目类别:
The mTOR and Hippo pathway in cell growth and cancer
mTOR 和 Hippo 通路在细胞生长和癌症中的作用
- 批准号:
9752481 - 财政年份:2015
- 资助金额:
$ 48.8万 - 项目类别:
The mTOR and Hippo pathway in cell growth and cancer
mTOR 和 Hippo 通路在细胞生长和癌症中的作用
- 批准号:
9120339 - 财政年份:2015
- 资助金额:
$ 48.8万 - 项目类别:
Regulation of the Hippo pathway and its role in uveal melanoma
Hippo通路的调节及其在葡萄膜黑色素瘤中的作用
- 批准号:
8722567 - 财政年份:2012
- 资助金额:
$ 48.8万 - 项目类别:
Regulation of the Hippo pathway and its role in uveal melanoma
Hippo通路的调节及其在葡萄膜黑色素瘤中的作用
- 批准号:
8529541 - 财政年份:2012
- 资助金额:
$ 48.8万 - 项目类别:
Regulation of the Hippo pathway and its role in uveal melanoma
Hippo通路的调节及其在葡萄膜黑色素瘤中的作用
- 批准号:
8340411 - 财政年份:2012
- 资助金额:
$ 48.8万 - 项目类别:
Protein phosphorylation and growth factor function
蛋白质磷酸化和生长因子功能
- 批准号:
7892688 - 财政年份:2009
- 资助金额:
$ 48.8万 - 项目类别:
Regulation and function of the YAP transcription co-activator oncoprotein
YAP转录辅激活癌蛋白的调控和功能
- 批准号:
8022881 - 财政年份:2008
- 资助金额:
$ 48.8万 - 项目类别:
Regulation and function of the YAP transcription co-activator oncoprotein
YAP转录辅激活癌蛋白的调控和功能
- 批准号:
8627562 - 财政年份:2008
- 资助金额:
$ 48.8万 - 项目类别:
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