Project-1: Defining the mechanisms by which neurons promote breast cancer metastasis
项目-1:定义神经元促进乳腺癌转移的机制
基本信息
- 批准号:10688115
- 负责人:
- 金额:$ 64.07万
- 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:2021-09-23 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAffectAutomobile DrivingBindingBiochemicalBlood VesselsBreast cancer metastasisCell LineCellsCoculture TechniquesComplexComputing MethodologiesDenervationDependenceDiseaseDisseminated Malignant NeoplasmDistantEndothelial CellsEndotheliumExtracellular Matrix ProteinsGeneticGoalsImageImmuneImmune systemImmunofluorescence ImmunologicImpairmentInfiltrationInterdisciplinary StudyInvadedLabelMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of prostateMammary NeoplasmsMechanicsMediatingMolecularMolecular ProbesNatureNeoplasm MetastasisNerveNeurobiologyNeuroepithelial, Perineurial, and Schwann Cell NeoplasmNeuronsNonmetastaticNutrientOxygenPatternPeripheralPhenotypePlayPopulationProcessProliferatingProteinsRNA-Binding ProteinsRecurrenceResearchResistanceRiskRoleSignal TransductionSkin CancerSystemTestingTumor Cell InvasionTumor PromotionTumor-infiltrating immune cellsWorkaxon guidancebreast cancer progressioncancer cellexperimental studyimaging studyin vivomalignant breast neoplasmmalignant stomach neoplasmmigrationnerve supplyneuralneural modelneuroregulationneurotransmissionneurotrophic factornew therapeutic targetperineuralpharmacologicresponsesingle cell sequencingtherapeutic targettherapy resistanttranscription factortumortumor initiationtumor microenvironmenttumor progressiontumorigenesis
项目摘要
Project Summary
Tumors are a heterogenous population of cancer cells, infiltrating host cells, secreted factors and extracellular
matrix proteins–together comprising the tumor microenvironment. The tumor microenvironment plays profound
roles in supporting tumor initiation, survival, progression and metastasis. We have discovered that tumor
endothelial cells provide an “instructive” signal to cancer cells that drives metastatic progression. We found Slit2,
an axon guidance molecule, to be upregulated in endothelial cells within metastatic tumors. Endothelial-specific
deletion of Slit2 strongly inhibited metastasis. In a surprising discovery, we found that endothelial-Slit2 deletion
also impairs tumor innervation. Nerves are only starting to be recognized as key players within the tumor stroma,
with recent evidence demonstrating their requirement for tumor initiation of gastric and prostate cancers. In
breast cancer, although there is some preliminary evidence that innervation correlates with tumor
aggressiveness, nerve dependence for metastasis has not been explored. In this Project, we will define the role
of neurons within the stroma of primary breast tumors and understand how neurons regulate metastasis. Using
isogenic cell lines of differential metastatic potential, retrograde tracing and imaging studies, we will first identify
neuronal sub-populations that regulate breast cancer metastasis. We will use 3D co-culture systems and in vivo
denervation experiments to identify the role of neurons in tumor invasion, proliferation, local and systemic
dissemination, distant seeding, and metastatic outgrowth. We will also evaluate the role of tumor innervation in
therapeutic resistance in breast cancer. Next, we will use unbiased sequencing approaches to define tumor-
trophic factors secreted by neurons and delineate downstream signaling axes in cancer cells. Finally, we will
characterize the role of endothelial cells in guiding neurons into metastatic tumors and determine if the pro-
metastatic effects of neurons are partly mediated by immune cells. The proposed inter-disciplinary research plan
combines molecular, genetic, biochemical, imaging and computational approaches to establish an integrated
model for neural regulation of metastatic progression by breast cancer. Collectively, these studies will define the
cellular and molecular interactions between endothelial cells, neurons, and immune cells within the tumor
microenvironment–an overarching goal of our proposed MetNet research center. These studies have
tremendous potential for impact as that they stand to identify novel therapeutic targets that perturb neural-tumoral
signaling axes driving metastasis.
项目总结
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 }}
Sohail F. Tavazoie其他文献
A commonly inherited human emPCSK9/em germline variant drives breast cancer metastasis via LRP1 receptor
一种常见的遗传性人类前蛋白转化酶枯草杆菌蛋白酶/kexin 型 9(PCSK9)种系变体通过低密度脂蛋白受体相关蛋白 1(LRP1)受体驱动乳腺癌转移
- DOI:
10.1016/j.cell.2024.11.009 - 发表时间:
2025-01-23 - 期刊:
- 影响因子:42.500
- 作者:
Wenbin Mei;Schayan Faraj Tabrizi;Christopher Godina;Anthea F. Lovisa;Karolin Isaksson;Helena Jernström;Sohail F. Tavazoie - 通讯作者:
Sohail F. Tavazoie
Neuronal substance P drives metastasis through an extracellular RNA–TLR7 axis
神经元 P 物质通过细胞外 RNA-TLR7 轴驱动转移
- DOI:
10.1038/s41586-024-07767-5 - 发表时间:
2024-08-07 - 期刊:
- 影响因子:48.500
- 作者:
Veena Padmanaban;Isabel Keller;Ethan S. Seltzer;Benjamin N. Ostendorf;Zachary Kerner;Sohail F. Tavazoie - 通讯作者:
Sohail F. Tavazoie
Endothelial-cell killing promotes metastasis
内皮细胞杀伤促进转移
- DOI:
10.1038/nature19465 - 发表时间:
2016-08-03 - 期刊:
- 影响因子:48.500
- 作者:
Claudio R. Alarcón;Sohail F. Tavazoie - 通讯作者:
Sohail F. Tavazoie
Transfer RNAs as dynamic and critical regulators of cancer progression
转运 RNA 作为癌症进展的动态且关键的调节因子
- DOI:
10.1038/s41568-023-00611-4 - 发表时间:
2023-10-09 - 期刊:
- 影响因子:66.800
- 作者:
Alexandra M. Pinzaru;Sohail F. Tavazoie - 通讯作者:
Sohail F. Tavazoie
Conserved genetic basis for microbial colonization of the gut
肠道微生物定殖的保守遗传基础
- DOI:
10.1016/j.cell.2025.03.010 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:42.500
- 作者:
Menghan Liu;Sydney B. Blattman;Mai Takahashi;Nandan Mandayam;Wenyan Jiang;Panos Oikonomou;Sohail F. Tavazoie;Saeed Tavazoie - 通讯作者:
Saeed Tavazoie
Sohail F. Tavazoie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('Sohail F. Tavazoie', 18)}}的其他基金
Project-1: Defining the mechanisms by which neurons promote breast cancer metastasis
项目 1:定义神经元促进乳腺癌转移的机制
- 批准号:
10493338 - 财政年份:2021
- 资助金额:
$ 64.07万 - 项目类别:
Project-1: Defining the mechanisms by which neurons promote breast cancer metastasis
项目 1:定义神经元促进乳腺癌转移的机制
- 批准号:
10271737 - 财政年份:2021
- 资助金额:
$ 64.07万 - 项目类别:
Regulation of metastatic progression by an endothelial-derived factor
内皮衍生因子对转移进展的调节
- 批准号:
10155448 - 财政年份:2019
- 资助金额:
$ 64.07万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 64.07万 - 项目类别:
Research Grant