Role of ER stress and fatty acid metabolism in glioma stem cells

内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用

基本信息

  • 批准号:
    10261413
  • 负责人:
  • 金额:
    $ 39.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-15 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Abstract Glioblastoma is the most malignant and common form of primary central nervous system tumors with high mortality and resistance to therapy. The presence of Glioma stem cells (GSCs) within the tumor, further complicates treatment, owing to the role of GSCs in promoting therapeutic resistance and tumor recurrence. Identifying Intrinsic and extrinsic factors that contribute to GSCs maintenance thus influencing tumor growth, could offer new therapeutic opportunities to treat this fatal disease. We recently showed that the desaturation of fatty acids (FA) is essential for maintaining GSCs self-renewal, proliferation, and in vivo tumor initiation properties. Pharmacological targeting of the desaturase enzyme Stearoyl CoA Desaturase 1 (SCD1) is particularly toxic due to the accumulation of saturated FA, which promotes apoptotic cell death, and achieves a remarkable therapeutic outcome in xenograft mouse models. Our results demonstrate that the dependence of GSCs on FA desaturation presents an exploitable vulnerability to target glioblastoma. However, regulation mechanisms driving key lipogenic enzymes such as SCD1, as well as the molecular role of FA in GSCs maintenance and plasticity remains unclear. Based on our preliminary results, we propose that stress signaling through the endoplasmic reticulum (ER stress), promotes the transcriptional activation of SCD1 as well as oncogenic signaling pathways downstream of SCD1 that are essential for GSCs maintenance. The objective of this proposal is to: 1) Define the role of ER stress in activating lipogenesis and oncogenic signaling that promote GSC self-renewal and increase tumorigenic potential. 2) Exploit the dependency of GSCs on adaptive ER stress signaling to test targeted therapeutics in patient-derived orthotopic GSCs mouse models. Upon completion, this work will elucidate novel mechanisms of plasticity and survival in GBM cancer stem cells and identify novel targeted therapeutics for clinical evaluation in GBM patients.
摘要

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 }}

Christian Elias Badr其他文献

Christian Elias Badr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('Christian Elias Badr', 18)}}的其他基金

Translocon-regulated ER proteostasis in glioblastoma
胶质母细胞瘤中易位蛋白调节的内质网蛋白稳态
  • 批准号:
    10301296
  • 财政年份:
    2021
  • 资助金额:
    $ 39.35万
  • 项目类别:
Role of ER Stress and Fatty Acid Metabolism in Glioma Stem Cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
  • 批准号:
    10665639
  • 财政年份:
    2020
  • 资助金额:
    $ 39.35万
  • 项目类别:
Screening for DNA damage response modulators in glioblastoma stem cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
  • 批准号:
    10038588
  • 财政年份:
    2020
  • 资助金额:
    $ 39.35万
  • 项目类别:
Role of ER stress and fatty acid metabolism in glioma stem cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
  • 批准号:
    10461146
  • 财政年份:
    2020
  • 资助金额:
    $ 39.35万
  • 项目类别:
Screening for DNA Damage Response Modulators in Glioblastoma Stem Cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
  • 批准号:
    10683338
  • 财政年份:
    2020
  • 资助金额:
    $ 39.35万
  • 项目类别:
Screening for DNA damage response modulators in glioblastoma stem cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
  • 批准号:
    10618739
  • 财政年份:
    2020
  • 资助金额:
    $ 39.35万
  • 项目类别:
Identifying vulnerabilities and therapeutic targets in Glioma Stem Cells
识别神经胶质瘤干细胞的脆弱性和治疗靶点
  • 批准号:
    8948656
  • 财政年份:
    2015
  • 资助金额:
    $ 39.35万
  • 项目类别:

相似海外基金

Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases
细胞中激活凋亡半胱天冬酶的生/死决策的机制
  • 批准号:
    10607815
  • 财政年份:
    2023
  • 资助金额:
    $ 39.35万
  • 项目类别:
Nuclear and chromatin aberrations during non-apoptotic cell death in C. elegans and mammals
线虫和哺乳动物非凋亡细胞死亡过程中的核和染色质畸变
  • 批准号:
    10723868
  • 财政年份:
    2023
  • 资助金额:
    $ 39.35万
  • 项目类别:
Non-apoptotic functions of caspase-3 in neural development
Caspase-3在神经发育中的非凋亡功能
  • 批准号:
    10862033
  • 财政年份:
    2023
  • 资助金额:
    $ 39.35万
  • 项目类别:
Apoptotic Donor Leukocytes to Promote Kidney Transplant Tolerance
凋亡供体白细胞促进肾移植耐受
  • 批准号:
    10622209
  • 财政年份:
    2023
  • 资助金额:
    $ 39.35万
  • 项目类别:
Design of apoptotic cell mimetic anti-inflammatory polymers for the treatment of cytokine storm
用于治疗细胞因子风暴的模拟凋亡细胞抗炎聚合物的设计
  • 批准号:
    22H03963
  • 财政年份:
    2022
  • 资助金额:
    $ 39.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Identifying the mechanisms behind non-apoptotic functions of mitochondrial matrix-localized MCL-1
确定线粒体基质定位的 MCL-1 非凋亡功能背后的机制
  • 批准号:
    10537709
  • 财政年份:
    2022
  • 资助金额:
    $ 39.35万
  • 项目类别:
Environmental Carcinogens Induce Minority MOMP to Initiate Carcinogenesis in Lung Cancer and Mesothelioma whileMaintaining Apoptotic Resistance via Mcl-1
环境致癌物诱导少数 MOMP 引发肺癌和间皮瘤的癌变,同时通过 Mcl-1 维持细胞凋亡抵抗
  • 批准号:
    10356565
  • 财政年份:
    2022
  • 资助金额:
    $ 39.35万
  • 项目类别:
Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
  • 批准号:
    10708827
  • 财政年份:
    2022
  • 资助金额:
    $ 39.35万
  • 项目类别:
Activation of non-apoptotic cell death by the DNA damage response
DNA 损伤反应激活非凋亡细胞死亡
  • 批准号:
    10388929
  • 财政年份:
    2022
  • 资助金额:
    $ 39.35万
  • 项目类别:
Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
  • 批准号:
    10538071
  • 财政年份:
    2022
  • 资助金额:
    $ 39.35万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了