Role of prolactin in adipocyte-breast cancer cell crosstalk
催乳素在脂肪细胞-乳腺癌细胞串扰中的作用
基本信息
- 批准号:10358133
- 负责人:
- 金额:$ 45.15万
- 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:2022-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AdipocytesAdipose tissueAffectAgonistAndrogensAromataseBiological MarkersBreastBreast Cancer CellBreast Cancer Risk FactorBreast Cancer cell lineBreast CarcinomaBreast biopsyCancer Cell GrowthCancer PrognosisCell physiologyCellsClinical ResearchDataDevelopmentEndocrineEstrogensEtiologyGoalsGrantGrowthGrowth FactorHealthHormonesHumanIncidenceInterleukin-6Interstitial CollagenaseJAK2 geneKnowledgeLeptinLinkLipidsMalignant Epithelial CellMammary Gland ParenchymaMammary NeoplasmsMammary glandMapsMediatingMetabolicMetabolismMissionMolecularMolecular TargetNeoplasm MetastasisObesityOutcomePAK-1 kinasePathway interactionsPatientsPhospho-Specific AntibodiesPhosphorylationPituitary GlandPostmenopauseProcessProlactinPublic HealthRegulationResearchResistanceRiskRoleSamplingSerineSignal PathwaySignal TransductionSystemTEC Protein Tyrosine KinaseTNF geneTestingThreonineTissuesTumorigenicityTyrosineUnited States National Institutes of HealthWorkadipokinesadiponectinbasebreast cancer diagnosiscancer cellcell motilitydiagnostic biomarkerdiagnostic toolepidemiology studyfatty acid oxidationhormone therapyin vivoinnovationinsightmalignant breast neoplasmmammarymigrationneoplastic cellnew therapeutic targetnovelnovel diagnosticsparacrineresponsestromelysin 3therapy resistanttooltumortumor behaviortumor growthtumor microenvironment
项目摘要
Project Summary/Abstract
There is a gap in our understanding of how hormone prolactin (PRL), secreted by adipocytes, and the
serine/threonine PAK1 connect to coordinately regulate progression of human breast cancer (BC) and
adipocyte-breast cancer cell crosstalk. The long-term goal of this research is to establish PAK1, activated by
adipocyte-secreted PRL, as a new diagnostic tool for the metastatic potential of BC cells and provide needed
insight into the underlying mechanisms. The overall objective of the current application is to establish an
experimental system to study effects of adipocyte-secreted PRL on breast cancer cells and adipocyte-breast
cancer cells crosstalk and further establish the mechanisms by which PRL-activated PAK1 contributes to
breast cancer. The central hypothesis is that that adipocyte-produced prolactin enhances invasiveness,
tumorigenicity and metastatic potential of breast cancer cells through activation of PAK1 kinase and pTyr-
PAK1 is a biomarker to predict metastatic potential of these breast cancer cells. The rational for the proposed
research is that breast adipocytes secret adipocytokines including PRL, which may influence breast tumor
behavior. PRL promotes JAK2 activation and tyrosyl phosphorylation of PAK1 in breast cancer cells. The
central hypothesis will be tested by pursuing the following specific aims: Specific Aim 1 will test our working
hypothesis that PAK1 activated by adipocyte-derived PRL enhances breast cancer cell invasiveness and cell
motility via Tec kinase and that adipocyte-breast cancer cells crosstalk induces secretion of MMP-11 by
adipocytes and MMP-1 by breast cancer cells. Specific Aim 2 will test our working hypothesis that PAK1
activated by adipocyte-derived PRL affects tumorigenicity and metastatic potential of breast cancer cells in vivo
and that pTyr-PAK1 can serve as a biomarker to predict breast tumor metastasis. Under the sub-aim,
characterized PAK1 phospho-specific antibodies will be used to evaluate metastatic potential of the cells at an
early stage of BC. This proposal is conceptually innovative because it is expected to vertically advance and
expand our understanding of how obesity through adipocyte-secreted PRL influences BC and the unique role
of PRL-activated PAK1 in this process. This proposal is technically innovative as well because it will employ
unique PAK1 phospho-specific antibodies. The proposed research is significant because the elucidation of
PRL/PAK1 mediated intracellular signaling pathways will enhance our understanding of the mechanisms
involved in regulation of BC and will lead to development of PAK1-based tools for BC diagnosis.
项目总结/文摘
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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MARIA DIAKONOVA其他文献
MARIA DIAKONOVA的其他文献
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{{ truncateString('MARIA DIAKONOVA', 18)}}的其他基金
Role of JAK2-PAK1 interaction in prolactin-dependent signaling
JAK2-PAK1 相互作用在催乳素依赖性信号传导中的作用
- 批准号:
8537914 - 财政年份:2010
- 资助金额:
$ 45.15万 - 项目类别:
Role of JAK2-PAK1 interaction in prolactin-dependent signaling
JAK2-PAK1 相互作用在催乳素依赖性信号传导中的作用
- 批准号:
8136055 - 财政年份:2010
- 资助金额:
$ 45.15万 - 项目类别:
Role of JAK2-PAK1 interaction in prolactin-dependent signaling
JAK2-PAK1 相互作用在催乳素依赖性信号传导中的作用
- 批准号:
7993282 - 财政年份:2010
- 资助金额:
$ 45.15万 - 项目类别:
Role of JAK2-PAK1 interaction in prolactin-dependent signaling
JAK2-PAK1 相互作用在催乳素依赖性信号传导中的作用
- 批准号:
8727530 - 财政年份:2010
- 资助金额:
$ 45.15万 - 项目类别:
Role of JAK2-PAK1 interaction in prolactin-dependent signaling
JAK2-PAK1 相互作用在催乳素依赖性信号传导中的作用
- 批准号:
8325709 - 财政年份:2010
- 资助金额:
$ 45.15万 - 项目类别:
Role of JAK2-PAK1 interaction in human breast cancer
JAK2-PAK1 相互作用在人类乳腺癌中的作用
- 批准号:
7515304 - 财政年份:2008
- 资助金额:
$ 45.15万 - 项目类别:
Role of the serine-threonine kinase PAK1 in prolactin-dependent signaling
丝氨酸-苏氨酸激酶 PAK1 在催乳素依赖性信号传导中的作用
- 批准号:
7275223 - 财政年份:2006
- 资助金额:
$ 45.15万 - 项目类别:
Role of the serine-threonine kinase PAK1 in prolactin-dependent signaling
丝氨酸-苏氨酸激酶 PAK1 在催乳素依赖性信号传导中的作用
- 批准号:
7277718 - 财政年份:2006
- 资助金额:
$ 45.15万 - 项目类别:
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