Store-Operated Calcium Entry in Tumor Invasion and Metastasis
肿瘤侵袭和转移中钙库控制的钙进入
基本信息
- 批准号:8629097
- 负责人:
- 金额:$ 34.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-12-03 至 2018-11-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingActinsArthritisAtherosclerosisBasement membraneCalciumCalcium ChannelCell membraneCellsCessation of lifeCharacteristicsDataDevelopmentDisseminated Malignant NeoplasmDistantDistant MetastasisExtracellular MatrixExtracellular Matrix DegradationFluorescence Resonance Energy TransferGoalsHumanImageImmunologic SurveillanceIntegrinsInterventionKnowledgeLifeLightMalignant NeoplasmsMediatingMelanoma CellMetastatic MelanomaMicroscopyModelingMolecularNeoplasm MetastasisOrganPathway interactionsPatientsPhysiologicalPrimary NeoplasmRecruitment ActivityRegulationReportingResearchResectedRoleSTIM1 geneSignal TransductionSpecificitySpecimenSpeedSuspension substanceSuspensionsSystemTestingTimeTissuesTumor Cell InvasionWorkXenograft procedurebonecancer cellcell motilitycellular imagingin vivoinhibitor/antagonistinsightmelanomamouse modelneoplastic cellnovelpublic health relevanceresearch studysensorsuccesstumor
项目摘要
PROJECT SUMMARY
Our long term goal is to define the mechanistic roles of store-operated calcium entry (SOCE) in tumor invasion
and metastasis. In this research plan we focus on the role of SOCE in the regulation of invadopodium
formation, extracellular matrix degradation and melanoma metastasis. Metastasis is responsible for more than
90% of cancer-related death and there are few treatment options available for metastatic cancer. One essential
characteristic for metastatic cells is enhanced motility and invasiveness, which helps tumor cells to overcome
barriers imposed by basement membrane and surrounding tissues. It is believed that tumor cells use
invadopodia to co-ordinate invasion and ECM degradation. Our recent preliminary studies in melanoma
support a model whereby SOCE is locally activated to initiate invadopodium formation, ECM degradation and
metastasis through a Ca2+-Pyk2-Src pathway. The expected results from Aim1 will define the spatio-temproal
organization of SOCE-mediated Ca2+ signals during invadpodium formation and 3D melanoma invasion. Since
the intricate organization of Ca2+ in space, time and concentration is the most critical aspect of Ca2+
mobilization that determines the speed, specificity and robustness of Ca2+ signals, and there is virtually no
report on the spatio-temporal regulation of Ca2+ signaling during tumor invasion or metastasis, our anticipated
results will bring significant insights into Ca2+ mobilization in disseminating melanoma cells. The successful
completion of Aim 2 and 3 will define a novel SOCE-Pyk2-Src pathway in melanoma invasion and metastasis
and shed new lights on how deregulated SOCE promote melanoma progression. Importantly, we will use novel
selective SOCE blocker GSK-7975A to inhibit the invasion and metastasis of human melanoma single cell
suspensions directly isolated from patients with metastatic melanoma. The success of the proposed study will
provide a proof of concept for targeting SOCE pathway to intervening melanoma metastasis.
项目总结
项目成果
期刊论文数量(0)
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Shengyu Yang其他文献
Shengyu Yang的其他文献
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{{ truncateString('Shengyu Yang', 18)}}的其他基金
Store-Operated Calcium Entry in Tumor Invasion and Metastasis
肿瘤侵袭和转移中钙库控制的钙进入
- 批准号:
8777949 - 财政年份:2013
- 资助金额:
$ 34.96万 - 项目类别:
Store-operated calcium entry in tumor invasion and metastasis
肿瘤侵袭和转移中钙库操纵的钙进入
- 批准号:
9292921 - 财政年份:2013
- 资助金额:
$ 34.96万 - 项目类别:
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