Functional role of PGAM5 in epithelial homeostasis and colorectal cancer
PGAM5 在上皮稳态和结直肠癌中的功能作用
基本信息
- 批准号:414209099
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2018
- 资助国家:德国
- 起止时间:2017-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Colorectal cancer (CRC) is the second leading cause of death from cancer worldwide. Aside from CRC developing spontaneously, especially in elderly patients, there is an increased risk for colorectal cancer in patients with inflammatory bowel disease (IBD). Both CRC and IBD occur in genetically susceptible individuals through poorly understood mechanisms and involve dysregulation of intestinal epithelial homeostasis. We have identified the molecule PGAM5 as a novel key factor of gut homeostasis and cell survival. PGAM5 is a mitochondrial phosphatase which might serve as a platform connecting several cell death pathways to mitochondrial stress and dynamics.PGAM5-deficient animals were more susceptible to epithelial cell death and loss of gut tissue homeostasis. Of note, our preliminary findings and initial proteomics data suggest a role of PGAM5 in the development of CRC. Our data demonstrate that PGAM5 is strongly up-regulated in both human and mouse CRC. PGAM5-deficient cancer cells showed a significant reduction in the Wnt/ beta-catenin signaling. On the basis of our preliminary data, we therefore hypothesize that PGAM5 plays an important role in CRC and gut homeostasis. However, the molecular mechanism by which PGAM5 exerts these function and the signaling pathway involved in these processes are yet to be defined. In order to better understand the functional role of PGAM5 in gut tissues homeostasis and colorectal cancer development, we seek to study PGAM5 using experimental mouse models for CRC and to identify relevant pathways and interaction partners of PGAM5 in intestinal epithelial cells. In four work packages we will first identify the functional role of PGAM5 in intestinal epithelial cell homeostasis and in experimental models of spontaneous and inflammation-dependent colorectal cancer. We will further determine PGAM5 regulated genes and pathways in intestinal epithelial cells and cancer cells. Finally, in a translational approach we will evaluate our findings for the relevance to human colorectal cancer using patient tissues and a sophisticate xenograft model. Our ultimate goal is an improved understanding of the function of PGAM5 in tissue homeostasis and colorectal cancer. We are confident to uncover whether influencing PGAM5 expression or function in CRC might be therapeutically effective.
结直肠癌(CRC)是全球癌症死亡的第二大原因。除了结直肠癌自发发展外,特别是在老年患者中,炎症性肠病(IBD)患者患结直肠癌的风险增加。结直肠癌和IBD都发生在遗传易感的个体中,其机制尚不清楚,并涉及肠上皮稳态失调。我们已经发现PGAM5分子是肠道稳态和细胞存活的一个新的关键因素。PGAM5是一种线粒体磷酸酶,可能作为连接线粒体应激和动力学的几种细胞死亡途径的平台。缺乏pgam5的动物更容易发生上皮细胞死亡和肠道组织稳态的丧失。值得注意的是,我们的初步研究结果和最初的蛋白质组学数据表明PGAM5在CRC的发展中起作用。我们的数据表明,PGAM5在人和小鼠CRC中都被强烈上调。缺乏pgam5的癌细胞显示Wnt/ β -连环蛋白信号显著减少。基于我们的初步数据,我们假设PGAM5在结直肠癌和肠道稳态中起重要作用。然而,PGAM5发挥这些功能的分子机制以及参与这些过程的信号通路尚未明确。为了更好地了解PGAM5在肠道组织稳态和结直肠癌发展中的功能作用,我们寻求使用CRC实验小鼠模型研究PGAM5,并确定PGAM5在肠上皮细胞中的相关途径和相互作用伙伴。在四个工作包中,我们将首先确定PGAM5在肠上皮细胞稳态和自发性和炎症依赖性结直肠癌实验模型中的功能作用。我们将进一步确定PGAM5在肠上皮细胞和癌细胞中的调控基因和通路。最后,在翻译方法中,我们将使用患者组织和复杂的异种移植模型来评估我们的发现与人类结直肠癌的相关性。我们的最终目标是进一步了解PGAM5在组织稳态和结直肠癌中的功能。我们有信心揭示影响PGAM5在结直肠癌中的表达或功能是否可能具有治疗效果。
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 }}
Professor Dr. Christoph Becker其他文献
Professor Dr. Christoph Becker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('Professor Dr. Christoph Becker', 18)}}的其他基金
Pathogenesis and Therapy of Ulcerative Colitis - From Sequence to Mechanisms
溃疡性结肠炎的发病机制和治疗——从序列到机制
- 批准号:
418055832 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Research Grants
Functional role of Smad7 on intestinal epithelial homeostasis and colorectal cancer development
Smad7 对肠上皮稳态和结直肠癌发展的功能作用
- 批准号:
319451951 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Units
Supportive project for the coordination of the Clinical Research Unit
临床研究单位协调支持项目
- 批准号:
275747348 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Clinical Research Units
Cytokine mediated mechanisms In the immunopathogenesis of inflammatory bowel diseases
炎症性肠病免疫发病机制中的细胞因子介导机制
- 批准号:
206954305 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Clinical Research Units
Investigation of caspase-8 regulation and function in the development of colorectal cancer
Caspase-8在结直肠癌发生过程中的调控和功能研究
- 批准号:
196244502 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Research Grants
Koordination der Klinischen Forschungsgruppe 257
临床研究小组的协调 257
- 批准号:
206968196 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Clinical Research Units
Role of enteric nervous system homeostasis in gut-nervous system immune signaling
肠神经系统稳态在肠道神经系统免疫信号传导中的作用
- 批准号:
516179478 - 财政年份:
- 资助金额:
-- - 项目类别:
Clinical Research Units
Characterization and function of OPA1 in intestinal epithelial homeostasis and the pathogenesis of inflammatory bowel disease
OPA1 在肠上皮稳态中的特征和功能以及炎症性肠病的发病机制
- 批准号:
510624836 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
Role of Epithelial Cell Death for Re-Establishment of the Gut Barrier During Resolution of Intestinal Inflammation
上皮细胞死亡在肠道炎症消退过程中重建肠道屏障的作用
- 批准号:
536563567 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
相似国自然基金
PfAP2-R介导的PfCRT转录调控在恶性疟原虫对喹啉类药物抗性中的作用及机制研究
- 批准号:82372275
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
Sestrin2抑制内质网应激对早产儿视网膜病变的调控作用及其机制研究
- 批准号:82371070
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
相似海外基金
The role of youth voluntary actions in Disaster Risk Reduction in the Ganges Brahmaputra and Meghna (GBM) delta
青年志愿行动在雅鲁藏布江和梅格纳河三角洲减少灾害风险中的作用
- 批准号:
2593674 - 财政年份:2025
- 资助金额:
-- - 项目类别:
Studentship
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
- 批准号:
2400967 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
Postdoctoral Fellowship: EAR-PF: Assessing the net climate impact of tropical peatland restoration: the role of methane
博士后奖学金:EAR-PF:评估热带泥炭地恢复对气候的净影响:甲烷的作用
- 批准号:
2305578 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship Award
NSF Postdoctoral Fellowship in Biology: Understanding the role of dietary toxins in shaping microbial community dynamics in the gut
NSF 生物学博士后奖学金:了解膳食毒素在塑造肠道微生物群落动态中的作用
- 批准号:
2305735 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship Award
NSF Postdoctoral Fellowship in Biology: Investigating the role of thermal stress response in facilitating adaptation in camel spiders
美国国家科学基金会生物学博士后奖学金:研究热应激反应在促进骆驼蜘蛛适应中的作用
- 批准号:
2305969 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship Award
Collaborative Research: New to IUSE: EDU DCL:Diversifying Economics Education through Plug and Play Video Modules with Diverse Role Models, Relevant Research, and Active Learning
协作研究:IUSE 新增功能:EDU DCL:通过具有不同角色模型、相关研究和主动学习的即插即用视频模块实现经济学教育多元化
- 批准号:
2315700 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
Size matters, but at what cost? Role of male sex hormones in the placenta
规模很重要,但代价是什么?
- 批准号:
DP240102256 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Discovery Projects
What is the role of striatal dopamine in value-based decision-making?
纹状体多巴胺在基于价值的决策中发挥什么作用?
- 批准号:
DP240103246 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Discovery Projects
Understanding the role of trauma in alcohol and other drug-related problems
了解创伤在酒精和其他毒品相关问题中的作用
- 批准号:
DP240101473 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Discovery Projects
Investigating the Role of International Higher Education in Japan-UK Relations: An Analysis of the RENKEI University Network Partnership
调查国际高等教育在日英关系中的作用:仁庆大学网络伙伴关系分析
- 批准号:
24K16704 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists