Methionine Dependency of Cancer
癌症的蛋氨酸依赖性
基本信息
- 批准号:10016225
- 负责人:
- 金额:$ 16.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-11 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimal ModelAnimalsApoptosisBehaviorBetaineBindingBiologicalBiological MarkersCRISPR/Cas technologyCancer Cell GrowthCarbonCell Cycle ArrestCell ProliferationCell SurvivalCellsCholineChromatinClinicClinicalClinical TrialsClustered Regularly Interspaced Short Palindromic RepeatsCoinCombined Modality TherapyComplexCulture MediaCysteineDataDefectDependenceDietDietary InterventionDropsEssential Amino AcidsFolic AcidGlutathione DisulfideGrowthHomeostasisHomocysteineHumanIndividualIsoleucineKnock-outLibrariesLinkMalignant NeoplasmsMass Spectrum AnalysisMediatingMediator of activation proteinMembraneMetabolicMetabolic PathwayMetabolismMethionineMethionine Metabolism PathwayMethylationModalityMolecularNormal CellPathway interactionsPatientsPharmaceutical PreparationsPhasePhospholipidsPhosphoric Monoester HydrolasesPlasmaPositron-Emission TomographyProliferatingProtein Phosphatase 2A Regulatory Subunit PR53RNARNA CapsRattusReducing dietReportingS-AdenosylhomocysteineS-AdenosylmethionineSeriesSerumSolid NeoplasmStressSupplementationTherapeuticThionesTissuesTranslationsValinebasecancer cellcancer therapydietary restrictionexperimental studygenome-widekinase inhibitorleukemiametabolomicsmethionylmethioninepotential biomarkerresponsescreeningsmall moleculetumortumor growth
项目摘要
Project Summary
Over 30 years ago it was discovered that cancer cells show a unique metabolic requirement for
methionine that separates them from normal cells. This phenomenon is called “methionine
dependence of cancer” or “methionine sensitivity of cancer” and describes the growth behavior of
cancer cells when methionine is replaced with its immediate metabolic precursor homocysteine. While
non-tumorigenic cells proliferate at normal rates in homocysteine medium, the overwhelming majority
of cancer cells induces cell cycle arrest followed by apoptosis when cultured in homocysteine
conditions. While conversion of homocysteine to methionine is not defective in cancer cells, these
growth conditions appear to reduce the flux through the one-carbon cycle, which seems to primarily
affect cancer cell growth. The dependence on high metabolic flux through methionine metabolism is
also observed in solid tumors and leukemias. While the phenomenon of methionine sensitivity of
cancer promises great therapeutic potential, it has been difficult to sufficiently reduce methionine
availability in patients to trigger tumor regression through dietary restrictions alone. It is thus essential
to understand the underlying mechanisms that govern methionine dependence of cancer. We
therefore respond to the NCI’s provocative question 11 (Through what mechanisms do diet and
nutritional interventions affect the response to cancer treatment?) and aim to understand molecular
mechanisms that trigger methionine sensitivity of cancer, and discover treatment modalities that are
enhanced by reduced methionine availability.
项目摘要
30多年前,人们发现癌细胞显示出独特的代谢需求,
甲硫氨酸将它们与正常细胞分开。这种现象被称为“甲硫氨酸
癌症的甲硫氨酸依赖性”或“癌症的甲硫氨酸敏感性”,并描述了
当蛋氨酸被其直接代谢前体同型半胱氨酸取代时,癌细胞中的蛋氨酸会发生变化。而
非致瘤细胞在同型半胱氨酸培养基中以正常速率增殖,绝大多数
当在同型半胱氨酸中培养时,
条件虽然高半胱氨酸向甲硫氨酸的转化在癌细胞中没有缺陷,但这些缺陷在癌细胞中并不存在。
生长条件似乎减少了通过一碳循环的通量,这似乎主要是
影响癌细胞生长。通过甲硫氨酸代谢对高代谢通量的依赖是
也在实体瘤和白血病中观察到。而甲硫氨酸敏感现象
癌症有巨大的治疗潜力,但很难充分减少蛋氨酸
在患者中,仅通过饮食限制就可以触发肿瘤消退。因此,
了解控制癌症的蛋氨酸依赖性的潜在机制。我们
因此,对NCI的挑衅性问题11(通过什么机制饮食和
营养干预影响对癌症治疗的反应?)并致力于了解分子
触发癌症的甲硫氨酸敏感性的机制,并发现
通过降低蛋氨酸的可用性而增强。
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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Peter Kaiser其他文献
Peter Kaiser的其他文献
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{{ truncateString('Peter Kaiser', 18)}}的其他基金
Developing corrector small molecules for reactivation of mutant p53 in cancer
开发用于重新激活癌症中突变 p53 的校正小分子
- 批准号:
10512976 - 财政年份:2022
- 资助金额:
$ 16.8万 - 项目类别:
Developing corrector small molecules for reactivation of mutant p53 in cancer
开发用于重新激活癌症中突变 p53 的校正小分子
- 批准号:
10675004 - 财政年份:2022
- 资助金额:
$ 16.8万 - 项目类别:
Molecular concepts that monitor methionine metabolism
监测蛋氨酸代谢的分子概念
- 批准号:
9892665 - 财政年份:2018
- 资助金额:
$ 16.8万 - 项目类别:
Regulation by Proteolysis-Independent Ubiquitination
不依赖蛋白水解的泛素化调节
- 批准号:
7854558 - 财政年份:2009
- 资助金额:
$ 16.8万 - 项目类别:
Identification of Small Molecules for Reactivation of p53 Cancer Mutants
鉴定用于 p53 癌症突变体再激活的小分子
- 批准号:
7617518 - 财政年份:2008
- 资助金额:
$ 16.8万 - 项目类别:
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