Gain-of-function mutant p53 and metabolic reprogramming in colorectal cancer
结直肠癌中的功能获得突变体 p53 和代谢重编程
基本信息
- 批准号:10231719
- 负责人:
- 金额:$ 44.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:ApcMin/+ miceAutomobile DrivingBiologicalClinicalColorectal CancerColorectal NeoplasmsDevelopmentEnzymesEventFASN geneFatty AcidsGoalsHomeostasisHumanKnock-in MouseLipidsMalignant NeoplasmsMediatingMetabolicMetabolismModelingMusMutateMutationNude MiceOncogenicPhosphorylationPlayPreventionProteinsProteomicsRegulationResolutionRoleSamplingTP53 geneTestingTherapeuticTumor SuppressionUbiquitinationWorkbasecancer cellcancer therapychemical carcinogenchemotherapycolon tumorigenesiscolorectal cancer progressioncolorectal cancer treatmentconditional knockoutgain of functionliquid chromatography mass spectrometrymetabolomicsmouse modelmutantnew therapeutic targetnovelphosphoproteomicssmall hairpin RNAsmall molecule inhibitortargeted cancer therapytargeted treatmenttranscriptome sequencingtumortumor progressiontumorigenesis
项目摘要
Tumor suppressor p53 plays a central role in tumor prevention. p53 is frequently mutated in human cancer,
including colorectal cancer (CRC). Many mutant p53 (mutp53) proteins not only lose tumor suppressive
function of wild-type p53, but also gain new oncogenic activities to promote tumorigenesis, which is defined as
mutp53 gain-of-function (GOF). Maintaining metabolic homeostasis is a novel and critical mechanism of p53 in
tumor suppression. Cancer cells often display lipid metabolic reprogramming, which contributes greatly to
cancer progression. Currently, the role and mechanism of mutp53 in cancer metabolic reprogramming are
poorly defined. Our preliminary studies suggest that mutp53 drives lipid metabolic reprogramming as a critical
GOF in CRC cells, and targeting lipid metabolic reprogramming compromises mutp53 GOF in colorectal
tumorigenesis. Based on our preliminary results, we hypothesize that GOF mutp53 drives lipid metabolic
reprogramming as a critical mechanism to promote colorectal tumorigenesis, which can be targeted for therapy
in CRC carrying mutp53. In this proposed study, we will determine the role (Aim 1) and mechanism (Aim 2) of
GOF mutp53 in driving lipid metabolic reprogramming in CRC. We will further assess targeting mutp53-driven
lipid metabolic reprogramming as a potential therapeutic strategy for CRC carrying mutp53 (Aim 3). The goal
of this study is to determine the mechanism of GOF mutp53 in CRC to provide effective targets and strategies
for CRC therapy. Metabolic reprogramming and p53 mutations are common events in cancer, and have
become extremely attractive targets for cancer therapy. We expect that the results from this proposed study
will deepen our understanding of the role and mechanism of mutp53 in metabolic reprogramming and
tumorigenesis, and provide the rationale and base for the development of new therapeutic targets and
strategies for cancers carrying mutp53.
肿瘤抑制因子p53在肿瘤预防中起着重要作用。p53在人类癌症中经常突变,
包括结肠直肠癌(CRC)。许多突变型p53(mutp53)蛋白不仅失去了肿瘤抑制作用,
野生型p53的功能,但也获得新的致癌活性,以促进肿瘤发生,这被定义为
mutp53功能获得性(GOF)。维持代谢稳态是p53在细胞内的一种新的和关键的机制。
肿瘤抑制癌细胞通常表现出脂质代谢重编程,这极大地促进了癌症的发生。
癌症进展目前,mutp53在肿瘤代谢重编程中的作用和机制是
定义不好。我们的初步研究表明,mutp53驱动脂质代谢重编程作为一个关键的
CRC细胞中的GOF,以及靶向脂质代谢重编程损害结直肠癌中的mutp53 GOF
肿瘤发生基于我们的初步结果,我们假设GOF mutp53驱动脂质代谢,
重编程是促进结直肠肿瘤发生的关键机制,可用于靶向治疗
在CRC中携带mutp53。在这项拟议的研究中,我们将确定的作用(目标1)和机制(目标2),
GOF mutp53驱动CRC中的脂质代谢重编程。我们将进一步评估靶向mutp53驱动的
脂质代谢重编程作为携带mutp53的CRC的潜在治疗策略(目的3)。目标
本研究的目的是探讨GOF mutp53在大肠癌中的作用机制,为临床治疗大肠癌提供有效的靶点和策略
用于CRC治疗。代谢重编程和p53突变是癌症中常见的事件,
成为非常有吸引力的癌症治疗靶点。我们希望这项研究的结果
将加深我们对mutp53在代谢重编程中的作用和机制的理解,
为开发新的治疗靶点提供理论依据和基础,
携带mutp53的癌症的策略。
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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Zhaohui Feng其他文献
Zhaohui Feng的其他文献
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{{ truncateString('Zhaohui Feng', 18)}}的其他基金
The regulation of mutant p53 protein accumulation in cancer: molecular basis and therapeutic potential
癌症中突变 p53 蛋白积累的调节:分子基础和治疗潜力
- 批准号:
10315918 - 财政年份:2021
- 资助金额:
$ 44.01万 - 项目类别:
The regulation of mutant p53 protein accumulation in cancer: molecular basis and therapeutic potential
癌症中突变 p53 蛋白积累的调节:分子基础和治疗潜力
- 批准号:
10406369 - 财政年份:2021
- 资助金额:
$ 44.01万 - 项目类别:
Gain-of-function mutant p53 and metabolic reprogramming in colorectal cancer
结直肠癌中的功能获得突变体 p53 和代谢重编程
- 批准号:
10589842 - 财政年份:2021
- 资助金额:
$ 44.01万 - 项目类别:
Gain-of-function mutant p53 and metabolic reprogramming in colorectal cancer
结直肠癌中的功能获得突变体 p53 和代谢重编程
- 批准号:
10378007 - 财政年份:2021
- 资助金额:
$ 44.01万 - 项目类别:
The regulation of mutant p53 protein accumulation in cancer: molecular basis and therapeutic potential
癌症中突变 p53 蛋白积累的调节:分子基础和治疗潜力
- 批准号:
10622593 - 财政年份:2021
- 资助金额:
$ 44.01万 - 项目类别:
SENP6, a novel p53 negative regulator, is an important new player in cancer
SENP6 是一种新型 p53 负调节因子,是癌症中重要的新参与者
- 批准号:
10197830 - 财政年份:2018
- 资助金额:
$ 44.01万 - 项目类别:
SENP6, a novel p53 negative regulator, is an important new player in cancer
SENP6 是一种新型 p53 负调节因子,是癌症中重要的新参与者
- 批准号:
10418636 - 财政年份:2018
- 资助金额:
$ 44.01万 - 项目类别:
The role of glutaminase 2, a novel p53 target gene in metabolism, in liver cancer
代谢中新型 p53 靶基因谷氨酰胺酶 2 在肝癌中的作用
- 批准号:
8033693 - 财政年份:2010
- 资助金额:
$ 44.01万 - 项目类别:
The role of glutaminase 2, a novel p53 target gene in metabolism, in liver cancer
代谢中新型 p53 靶基因谷氨酰胺酶 2 在肝癌中的作用
- 批准号:
8699974 - 财政年份:2010
- 资助金额:
$ 44.01万 - 项目类别:
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