Functional interplay between Hippo and estrogen receptor ESR1
Hippo 和雌激素受体 ESR1 之间的功能相互作用
基本信息
- 批准号:10573162
- 负责人:
- 金额:$ 42.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressBiologyBreast Cancer CellBreast Cancer TreatmentBreast Cancer therapyDevelopmentESR1 geneEstrogen ReceptorsEstrogen declineEstrogen receptor positiveGene Expression RegulationGoalsGrowthHomeostasisHumanImmunotherapyLATS1 geneLaboratoriesMalignant NeoplasmsMammary Gland ParenchymaMediatingMedicalMolecularNuclearOrgan SizePathway interactionsPhosphotransferasesPlayReceptor GeneRegulationRoleSignal TransductionTherapeutic InterventionTissuesTranscriptional Regulationcancer cellcell growthdrug resistance developmenthormone therapyimmunogenicitymalignant breast neoplasmnovelnovel therapeuticstherapy resistanttranscription factortumorigenesis
项目摘要
Functional interplay between Hippo and estrogen receptor ESR1
Project Summary/Abstract
The majority of breast cancers are estrogen receptor (ER positive and growth of ER+
cancer is dependent on ER function. Hormone therapy by inhibiting ER is most commonly used
for ER+ breast cancer treatment, however, drug resistance develops. There is strong medical
need to develop new therapy, particularly for hormone therapy resistant breast cancer. Estrogen
receptor 1 (ESR1) encodes the major form of ER and has been extensively studied for its function
as a nuclear transcription factor. However, the transcriptional regulation of ESR1 itself is less
understood. Preliminary studies from our laboratory have shown that ESR1 expression is tightly
controlled by the Hippo pathway, which is known for its role in organ size control and
tumorigenesis. Deletion of LATS1/2 kinases, core components of the Hippo pathway, abolishes
ESR1 expression and inhibits growth of ER+ breast cancer cells. We further discovered that
LATS1/2 suppress cancer cell immunogenicity. This proposal is based on our novel and exciting
observations. A major goal of this project is to reveal the molecular mechanism of ESR1
transcription regulation by the Hippo pathway and the functional significance of ESR1 in mediating
Hippo biology in breast tissue. Furthermore, we posit that LATS inhibition has two effects on ER+
breast cancer: suppression of cell growth by reducing ESR1 expression; and enhancing the
efficacy of immunotherapy by increasing cancer cell immunogenicity. The second major goal is
to provide scientific basis for targeting the LATS1/2 kinases as a novel therapy for ER+ breast
cancer.
Hippo 和雌激素受体 ESR1 之间的功能相互作用
项目概要/摘要
大多数乳腺癌是雌激素受体(ER 阳性且 ER+ 生长)
癌症取决于 ER 功能。最常用的是抑制 ER 的激素疗法
然而,对于 ER+ 乳腺癌治疗,会产生耐药性。有雄厚的医疗实力
需要开发新的疗法,特别是针对激素疗法耐药的乳腺癌。雌激素
受体 1 (ESR1) 编码 ER 的主要形式,其功能已被广泛研究
作为核转录因子。但ESR1本身的转录调控作用较少
明白了。我们实验室的初步研究表明ESR1表达紧密
由 Hippo 通路控制,该通路以其在器官大小控制和
肿瘤发生。删除 LATS1/2 激酶(Hippo 通路的核心成分)可消除
ESR1 表达并抑制 ER+ 乳腺癌细胞的生长。我们进一步发现
LATS1/2 抑制癌细胞免疫原性。这个提案是基于我们新颖而令人兴奋的
观察。该项目的一个主要目标是揭示ESR1的分子机制
Hippo 通路的转录调控及 ESR1 在介导中的功能意义
乳腺组织中的河马生物学。此外,我们假设 LATS 抑制对 ER+ 有两个影响
乳腺癌:通过降低 ESR1 表达来抑制细胞生长;并增强
通过增加癌细胞免疫原性来提高免疫治疗的功效。第二个主要目标是
为靶向 LATS1/2 激酶作为 ER+ 乳腺的新型疗法提供科学依据
癌症。
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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Jing Yang其他文献
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