MnSOD-K68-Ac reprograms a lineage plasticity switch / stemness in ER+ breast malignancies
MnSOD-K68-Ac 重新编程 ER 乳腺恶性肿瘤中的谱系可塑性开关/干性
基本信息
- 批准号:10327336
- 负责人:
- 金额:$ 36.08万
- 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:2021-01-09 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AcetylationAdjuvant TherapyBiological MarkersBiologyBreastBreast Cancer CellCell physiologyCellsCellular Metabolic ProcessChIP-seqChemicalsCisplatinClustered Regularly Interspaced Short Palindromic RepeatsComplexDataDoxorubicinDrug Metabolic DetoxicationEndocrineEquilibriumEstrogen receptor positiveEventExhibitsExposure toFatty acid glycerol estersFulvestrantGenesGrantKnock-outLeadLinkLysineMCF7 cellMalignant NeoplasmsMammary NeoplasmsMeasurementMeasuresMediatingMetabolicMetabolismMitochondriaModelingNatureOncogenicPathway interactionsPeroxidasesPhenotypePhysiologicalPost-Translational Protein ProcessingPropertyPublicationsReactive Oxygen SpeciesRecurrenceReporterResistanceRiskSOD2 geneSelective Estrogen Receptor ModulatorsSignal TransductionSirtuinsStainsSubgroupSuperoxidesSystemic TherapyT47DTamoxifenTechniquesTestingTimeTissue MicroarrayTumor PromotersWomanWorkXenograft Modelbasebreast malignanciescancer cellhigh riskhormone therapyin vivoknock-downmammarymimeticsmitochondrial metabolismmouse modelmutantneoplastic cellnew therapeutic targetnovelpatient derived xenograft modelpreventpublic databaseresponsesmall hairpin RNAstemstem cell biomarkersstem-like cellstemnesstargeted treatmenttherapy resistanttissue culturetranscriptome sequencingtumortumorigenesistumorigenic
项目摘要
SUMMARY
The dysregulation of mitochondrial networks responsible for maintaining normal metabolism is an
established hallmark of cancer and an early event in tumorigenesis. The disruption of cell metabolism
leads to accumulation of reactive oxygen species (ROS) and triggers maladaptive signaling that
disrupts metabolic balance, which can establish a tumorigenic and/or therapy resistant phenotype.
In this regard, a subgroup of estrogen receptor-positive (ER+) breast malignancies, which exhibit
increased ROS levels and a high risk of recurrence due to endocrine therapy, has been identified.
We recently found a novel mitochondrial signaling axis centered on manganese superoxide
dismutase (MnSOD), which when the acetylation (Ac) status of lysine 68 (K68-Ac) is altered, disrupts
cell metabolism, leading to aberrant ROS levels (Zhu, Nature Commun., 2019). In addition, breast
cancer cells expressing a MnSOD-K68-Ac mimic mutant (MnSODK68Q) exhibited increased HIF2α
(known to promote stemness-like properties), increased SOX2 and Oct4 (two established stem cell
biomarkers), leading to oncogenicity and pan resistance phenotype (PanR) to agents commonly
used in luminal B breast malignancies-implying that disruption of cell metabolism reprograms tumors
to exhibit a lineage plasticity phenotype. Based on our new data, our recent publication (Zhu et al,
Nature Commun. 2019), and work by others, it is hypothesized that dysregulated MnSOD biology,
due to aberrant/increased MnSOD-K68-Ac levels, disrupts normal cellular and mitochondrial
metabolism. This initiates metabolic reprogramming, via increased levels of HIF2α, leading to a cell
stemness-mediated tumor-permissive and/or PanR phenotype. Thus, we seek to further explore how
MnSOD-K68-Ac disrupts cell metabolism and promotes a stemness-like phenotype, leading to
oncogenicity and/or PanR. Finally, will GC4419 exposure, a chemical SOD detoxification mimic,
reverse the oncogenic and/or PanR phenotypes?
总结
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 }}
David Gius其他文献
David Gius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('David Gius', 18)}}的其他基金
Lineage Plasticity, due to Disruption of MnSOD Biology, drives resistance to Ionizing Radiation / Androgen Deprivation Therapy
由于 MnSOD 生物学的破坏,谱系可塑性驱动了对电离辐射/雄激素剥夺疗法的抵抗
- 批准号:
10737810 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
Lineage Plasticity, due to Disruption of MnSOD Biology, drives resistance to Ionizing Radiation / Androgen Deprivation Therapy
由于 MnSOD 生物学的破坏,谱系可塑性驱动了对电离辐射/雄激素剥夺疗法的抵抗
- 批准号:
10533472 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
Lineage Plasticity, due to Disruption of MnSOD Biology, drives resistance to Ionizing Radiation / Androgen Deprivation Therapy
由于 MnSOD 生物学的破坏,谱系可塑性驱动了对电离辐射/雄激素剥夺疗法的抵抗
- 批准号:
10390451 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
MnSOD-K68-Ac reprograms a lineage plasticity switch / stemness in ER+ breast malignancies.
MnSOD-K68-Ac 重新编程 ER 乳腺恶性肿瘤中的谱系可塑性开关/干性。
- 批准号:
10817556 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
Dys-regulation of the MnSOD-Ac-ROS-HIF2a axis promotes IR / Cisplatin resistance phenotype
MnSOD-Ac-ROS-HIF2a 轴的失调促进 IR/顺铂耐药表型
- 批准号:
10335424 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
MnSOD-K68-Ac reprograms a lineage plasticity switch / stemness in ER+ breast malignancies
MnSOD-K68-Ac 重新编程 ER 乳腺恶性肿瘤中的谱系可塑性开关/干性
- 批准号:
10541193 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
Lineage Plasticity, due to Disruption of MnSOD Biology, drives resistance to Ionizing Radiation / Androgen Deprivation Therapy
由于 MnSOD 生物学的破坏,谱系可塑性驱动了对电离辐射/雄激素剥夺疗法的抵抗
- 批准号:
10548835 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
Dys-regulation of the MnSOD-Ac-ROS-HIF2a axis promotes IR / Cisplatin resistance phenotype
MnSOD-Ac-ROS-HIF2a 轴的失调促进 IR/顺铂耐药表型
- 批准号:
10024964 - 财政年份:2017
- 资助金额:
$ 36.08万 - 项目类别:
Dys-regulation of the MnSOD-Ac-ROS-HIF2a axis promotes IR / Cisplatin resistance phenotype
MnSOD-Ac-ROS-HIF2a 轴的失调促进 IR/顺铂耐药表型
- 批准号:
9889066 - 财政年份:2017
- 资助金额:
$ 36.08万 - 项目类别:
Dys-regulation of the MnSOD-Ac-ROS-HIF2a axis promotes IR / Cisplatin resistance phenotype
MnSOD-Ac-ROS-HIF2a 轴的失调促进 IR/顺铂耐药表型
- 批准号:
9262705 - 财政年份:2017
- 资助金额:
$ 36.08万 - 项目类别:
相似海外基金
Countering sympathetic vasoconstriction during skeletal muscle exercise as an adjuvant therapy for DMD
骨骼肌运动期间对抗交感血管收缩作为 DMD 的辅助治疗
- 批准号:
10735090 - 财政年份:2023
- 资助金额:
$ 36.08万 - 项目类别:
The ESCAPE clinical trial of circulating tumor DNA to guide adjuvant therapy in chemo-resistant triple negative breast cancer
循环肿瘤 DNA 指导化疗耐药三阴性乳腺癌辅助治疗的 ESCAPE 临床试验
- 批准号:
494901 - 财政年份:2023
- 资助金额:
$ 36.08万 - 项目类别:
Operating Grants
A Type I Hybrid Effectiveness-Implementation Trial to Evaluate a Navigation-Based Multilevel Intervention to Decrease Delays Starting Adjuvant Therapy Among Patients with Head and Neck Cancer
一项 I 型混合有效性实施试验,用于评估基于导航的多级干预措施,以减少头颈癌患者开始辅助治疗的延迟
- 批准号:
10714537 - 财政年份:2023
- 资助金额:
$ 36.08万 - 项目类别:
Multi-modal machine learning to guide adjuvant therapy in surgically resectable colorectal cancer
多模式机器学习指导可手术切除结直肠癌的辅助治疗
- 批准号:
10588103 - 财政年份:2023
- 资助金额:
$ 36.08万 - 项目类别:
Efficacy of ethanol adjuvant therapy after resection of malignant soft tissue tumors
恶性软组织肿瘤切除术后乙醇辅助治疗的疗效
- 批准号:
22K09407 - 财政年份:2022
- 资助金额:
$ 36.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of immune response cells and development of novel adjuvant therapy for sublingual immunotherapy
免疫应答细胞的鉴定和舌下免疫治疗新型辅助疗法的开发
- 批准号:
21KK0287 - 财政年份:2022
- 资助金额:
$ 36.08万 - 项目类别:
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
Pursuing molecular biomarkers to guide adjuvant therapy for HPV+ head and neck cancers after transoral robotic surgery
寻找分子生物标志物来指导经口机器人手术后 HPV 头颈癌的辅助治疗
- 批准号:
10357120 - 财政年份:2022
- 资助金额:
$ 36.08万 - 项目类别:
Biomarker research using two prospective studies on preoperative and postoperative adjuvant therapy for pancreatic cancer
使用两项关于胰腺癌术前和术后辅助治疗的前瞻性研究进行生物标志物研究
- 批准号:
21K08700 - 财政年份:2021
- 资助金额:
$ 36.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Personalized Resistant Starch as an Adjuvant Therapy for Pediatric Inflammatory Bowel Disease
个性化抗性淀粉作为小儿炎症性肠病的辅助治疗
- 批准号:
437315 - 财政年份:2020
- 资助金额:
$ 36.08万 - 项目类别:
Studentship Programs
Tailored adjuvant therapy in POLE-mutated and p53-wildtype early stage endometrial cancer (TAPER)
POLE 突变和 p53 野生型早期子宫内膜癌 (TAPER) 的定制辅助治疗
- 批准号:
435603 - 财政年份:2020
- 资助金额:
$ 36.08万 - 项目类别:
Operating Grants