The role of MIRO2 in tumor cell invasion and metastasis
MIRO2在肿瘤细胞侵袭和转移中的作用
基本信息
- 批准号:10464387
- 负责人:
- 金额:$ 3.62万
- 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:2022-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-Dimensional4T1AblationAddressBindingBinding ProteinsBiological AssayBreast Cancer ModelBreast Cancer PatientBreast MelanomaBreast cancer metastasisCalciumCause of DeathCell DeathCell SurvivalCell physiologyCellsCessation of lifeCo-ImmunoprecipitationsDataDetectionDevelopmentDiseaseDistalDominant-Negative MutationEF-Hand DomainGTPase-Activating ProteinsGoalsGrowthGuanosine TriphosphateGuanosine Triphosphate PhosphohydrolasesImmunohistochemistryImmunoprecipitationIn VitroInjectionsKnockout MiceLigationMDA MB 231Malignant NeoplasmsMalignant neoplasm of pancreasMalignant neoplasm of prostateMass Spectrum AnalysisMatrix MetalloproteinasesMeasurementMediatingMessenger RNAMetastatic toMitochondriaMitochondrial Membrane ProteinModelingMolecularMyosin ATPaseMyosin S-2Neoplasm MetastasisNeurogliaNeuronsNormal tissue morphologyOrganOrganellesOuter Mitochondrial MembranePancreasPatientsPharmacologyPhenotypePrimary NeoplasmProcessProductionProliferation MarkerProstateRecombinant ProteinsRoleSamplingSecondary toSignal PathwaySignal TransductionSiteSmall Interfering RNASystemTertiary Protein StructureTestingTissuesTumor Cell InvasionUnited StatesWorkcell motilitycell typehazardin vitro Assayin vivoin vivo Modelin vivo imaging systeminterestknock-downlive cell imagingmRNA Expressionneoplastic cellnew therapeutic targetnovelnovel therapeuticsprostate cancer cell lineprotein functionrho GTP-Binding Proteinsrho GTPase-activating proteinsmall hairpin RNAtargeted treatmenttherapeutic targettraffickingtumortumor growthtumorigenesistumorigenic
项目摘要
Project Abstract/Summary
Cancer is the second leading cause of death in the United States. Overall survival for patients with tumors
that remain localized to the tissue of origin remain relatively high, while it is estimated that 90% of all cancer
related deaths are due to metastatic dissemination to secondary sites. This underscores the importance of
identifying signaling pathways that promote metastasis. Mitochondria are multifunctional organelles with
important roles in regulating many cellular processes outside of ATP production and are recognized for their
roles in tumorigenesis and metastasis. This project seeks to define a novel mechanism that promotes tumor cell
invasion and metastasis through a previously unidentified signaling pathway between Mitochondrial Rho GTPase
2 (MIRO2) and atypical myosin IXB (MYO9B).
MIRO2 is an outer-mitochondrial membrane protein that is a part of the MIRO subfamily of Ras GTPases.
MIROs were first characterized in neurons where they are involved in the anterograde and retrograde trafficking
of mitochondria. MIRO2 has been shown by several groups to be dispensable for mitochondrial trafficking in
many non-neuronal cell types. Our lab has previously shown that MIRO2 mRNA is enriched in tumorigenic
tissues in many tumor types when compared to normal tissue. Additionally, we have shown in prostate cancer
that MIRO2 is important in tumor cell viability, anchorage-dependent and -independent growth, and tumor growth
in vivo. Despite this initial evidence, it remains unknown if MIRO2 exclusively impacts the primary tumor or if this
is also important in metastasis. My initial results show that loss of MIRO2 reduces the invasive capacity of tumor
cells from many tumor types including breast, melanoma, pancreas, and prostate. Furthermore, I have shown
out of the top newly identified MIRO2 binding partners, loss of MYO9B reduces invasive capacity to the greatest
extent. MYO9B is known to control cell motility by localizing to the leading edge of migrating cells and inactivating
RhoA through MYO9B’s Rho GTPase activating protein (GAP) domain. Excitingly, I show that loss of both MIRO2
and MYO9B result in increased active RhoA. Given this evidence, I hypothesize MIRO2 promotes tumor cell
invasion and metastasis through positively regulating MYO9B GAP activity.
In this proposal I will 1) determine the role of MIRO2 in tumor cell invasion and metastasis and 2)
determine the mechanism in which MIRO2 regulates tumor cell invasion. This proposal will utilize many models
including, but not limited to: 2D/3D in vitro invasion systems, live cell imaging of migrating cells, in vivo breast
cancer metastasis models, cell-free GTPase assays, co-immunoprecipitation, and proximity ligation assays.
Overall, the goal of this proposal is to serve as the basis for the development of novel therapeutics to target
metastatic disease.
项目摘要/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 }}
Dillon Boulton其他文献
Dillon Boulton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('Dillon Boulton', 18)}}的其他基金
The role of MIRO2 in tumor cell invasion and metastasis
MIRO2在肿瘤细胞侵袭和转移中的作用
- 批准号:
10704512 - 财政年份:2022
- 资助金额:
$ 3.62万 - 项目类别:
相似国自然基金
益气活血法对4T1乳腺癌细胞肺转移及SDF-1/CXCR4生物轴的干预作用
- 批准号:81503517
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
固本抑瘤Ⅱ号祛邪、扶正组分不同时期应用对4T1乳腺癌细胞生长转移及mTOR通路介导的自噬作用差异研究
- 批准号:81202689
- 批准年份:2012
- 资助金额:23.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Differential proteome analysis identifies TGF-beta related pro-metastatic proteins in a 4T1 murine breast cancer model
差异蛋白质组分析鉴定 4T1 小鼠乳腺癌模型中的 TGF-β 相关促转移蛋白
- 批准号:
25871241 - 财政年份:2013
- 资助金额:
$ 3.62万 - 项目类别:
Grant-in-Aid for Young Scientists (B)














{{item.name}}会员




