ErbB3-miRNA axis in tumor metastasis of erbB2-positive breast cancer
erbB2 阳性乳腺癌肿瘤转移中的 ErbB3-miRNA 轴
基本信息
- 批准号:9342732
- 负责人:
- 金额:$ 35.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-KinaseAKT Signaling PathwayAttenuatedBioinformaticsBlocking AntibodiesBreast Cancer CellBreast Cancer PatientBreast cancer metastasisCancer BiologyCell SurvivalClinicalDataDevelopmentDistant MetastasisDown-RegulationDrug resistanceERBB2 geneEctopic ExpressionEpigenetic ProcessEpithelialGenesGoalsHumanIn VitroLightLiteratureMalignant NeoplasmsMammary NeoplasmsMediatingMediator of activation proteinMesenchymalMetastatic Neoplasm to the LungMethylationMicroRNAsModelingMolecularMouse Mammary Tumor VirusNeoplasm MetastasisOncogenicOutcomePathway interactionsPatient-Focused OutcomesPatientsPlayProspective cohortRetrospective cohortRoleSignal TransductionTestingTransgenic MiceTrastuzumabTreatment EfficacyTreatment FailureVimentinbasecancer therapycohortcombinatorialepigenetic regulationerbB-2 Receptorgain of functionhistone modificationimprovedin vivoinhibitor/antagonistinsightlapatinibloss of functionmalignant breast neoplasmnovelnovel strategiesnovel therapeuticsoutcome forecastoverexpressionpreventpromoterreceptorreceptor functionslugsmall hairpin RNAsrc-Family Kinasessurvivintargeted agenttargeted treatmenttherapeutic targettumortumor progression
项目摘要
Elevated expression of erbB3 receptor correlates with increased distant metastasis of breast cancers with
amplification and/or overexpression of erbB2 (HER2/neu), which occur in approximately 25-30% of invasive
breast cancers and are significantly associated with a worse prognosis in breast cancer patients. The erbB3
receptor frequently co-expresses and interacts with erbB2 in breast cancer to activate the oncogenic
signaling, especially the PI-3K/Akt pathway and Src kinase. ErbB3 serves as a co-receptor of erbB2 and
plays a critical role in the development of erbB2-overexpressing (erbB2+) breast cancer. Our recent data
reveal that overexpression of erbB3 decreases, and inhibition of erbB3 signaling with an erbB3 specific
shRNA, an anti-erbB3 blocking antibody (Ab), or an Akt inhibitor increases the levels of miR-203 and miR-
542-3p in erbB2+ breast cancer cells. Interestingly, both miR-203 and miR-542-3p have been identified as
tumor suppressive miRNAs, and are frequently downregulated due to promoter methylation in various human
cancers, including breast cancer. Bioinformatics analysis suggests that miR-203 and/or miR-542-3p target
several critical genes, including Survivin, ZEB1, ZEB2, Snail1, and/or Slug, responsible for drug resistance,
epithelial-mesenchymal transition (EMT), and tumor metastasis. We also discover an enhanced expression of
ZEB1, Snail1, Slug, and Vimentin upon ectopic expression of erbB3 in erbB2+ breast cancer cells. Thus, we
hypothesize that activation of erbB3 signaling promotes erbB2+ breast cancer metastasis via
epigenetic silencing of the tumor suppressive miR-203/miR-542-3p and effective inhibition of erbB3
will significantly suppress metastasis via induction of miR-203/miR-542-3p. We intend to define miR-
203 and miR-542-3p as the key downstream mediators of erbB3 signaling to enhance metastatic potential of
erbB2+ breast cancer cells by upregulating the EMT markers; and identify novel strategy/agents inhibiting
erbB3 to prevent or attenuate erbB2+ breast cancer metastasis via induction of miR-203/miR-542-3p.
erbB 3受体表达升高与乳腺癌远处转移增加相关,
erbB 2(HER 2/neu)扩增和/或过表达,发生在大约25-30%的侵袭性肿瘤中。
与乳腺癌患者的预后不良显著相关。erbB3
受体在乳腺癌中经常与erbB 2共表达并相互作用,以激活癌基因
信号转导,尤其是PI-3 K/Akt通路和Src激酶。ErbB 3作为erbB 2的共受体,
在erbB 2过表达(erbB 2+)乳腺癌的发展中起着关键作用。我们最近的数据
显示erbB 3的过度表达减少,并且用erbB 3特异性抑制erbB 3信号传导,
shRNA、抗erbB 3阻断抗体(Ab)或Akt抑制剂增加miR-203和miR-204的水平。
erbB 2+乳腺癌细胞中的542- 3 p。有趣的是,miR-203和miR-542- 3 p都被鉴定为
肿瘤抑制性miRNAs,并且在各种人类中由于启动子甲基化而经常下调,
癌症,包括乳腺癌。生物信息学分析表明miR-203和/或miR-542- 3 p靶向
几个关键基因,包括Survivin、ZEB 1、ZEB 2、Snail 1和/或Slug,负责耐药性,
上皮-间质转化(EMT)和肿瘤转移。我们还发现,
ZEB 1、Snail 1、Slug和波形蛋白对erbB 2+乳腺癌细胞中erbB 3异位表达的影响因此我们
假设erbB 3信号传导激活通过以下途径促进erbB 2+乳腺癌转移:
肿瘤抑制性miR-203/miR-542- 3 p的表观遗传沉默和erbB 3的有效抑制
将通过诱导miR-203/miR-542- 3 p显著抑制转移。我们打算定义miR-
203和miR-542- 3 p作为erbB 3信号传导的关键下游介质,以增强肿瘤的转移潜力。
通过上调EMT标志物来抑制erbB 2+乳腺癌细胞;并鉴定抑制erbB 2+乳腺癌细胞的新策略/试剂。
erbB 3通过诱导miR-203/miR-542- 3 p预防或减弱erbB 2+乳腺癌转移。
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 }}
Bolin Liu其他文献
Bolin Liu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('Bolin Liu', 18)}}的其他基金
HER3-PHF8 signaling axis in triple-negative breast cancer progression
三阴性乳腺癌进展中的 HER3-PHF8 信号轴
- 批准号:
10584868 - 财政年份:2022
- 资助金额:
$ 35.05万 - 项目类别:
ErbB3-miRNA axis in tumor metastasis of erbB2-positive breast cancer
erbB2 阳性乳腺癌肿瘤转移中的 ErbB3-miRNA 轴
- 批准号:
9174796 - 财政年份:2016
- 资助金额:
$ 35.05万 - 项目类别:
ErbB3-miRNA axis in tumor metastasis of erbB2-positive breast cancer
erbB2 阳性乳腺癌肿瘤转移中的 ErbB3-miRNA 轴
- 批准号:
9763330 - 财政年份:2016
- 资助金额:
$ 35.05万 - 项目类别:
Survivin-targeting miRNAs in erbB3 promotion of erbB2-positive breast cancer
生存素靶向 miRNA 在 erbB3 促进 erbB2 阳性乳腺癌中的作用
- 批准号:
8621261 - 财政年份:2014
- 资助金额:
$ 35.05万 - 项目类别:
Survivin-targeting miRNAs in erbB3 promotion of erbB2-positive breast cancer
生存素靶向 miRNA 在 erbB3 促进 erbB2 阳性乳腺癌中的作用
- 批准号:
8804923 - 财政年份:2014
- 资助金额:
$ 35.05万 - 项目类别:
相似海外基金
Myocardial preconditioning effects of amino acids and PI3K/Akt signaling pathway
氨基酸和PI3K/Akt信号通路的心肌预适应作用
- 批准号:
16K10955 - 财政年份:2016
- 资助金额:
$ 35.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Myocardial preconditioning effects of high-dose insulin and PI3K/Akt signaling pathway
大剂量胰岛素及PI3K/Akt信号通路对心肌的预处理作用
- 批准号:
25462429 - 财政年份:2013
- 资助金额:
$ 35.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional analysis of the PI3K/Akt signaling pathway during the mammalian inner ear development and its application for regenerative medicine
哺乳动物内耳发育过程中PI3K/Akt信号通路的功能分析及其在再生医学中的应用
- 批准号:
23592496 - 财政年份:2011
- 资助金额:
$ 35.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of regulatory mechanism of PI3K-Akt signaling pathway by TTC3
TTC3对PI3K-Akt信号通路的调控机制分析
- 批准号:
22770118 - 财政年份:2010
- 资助金额:
$ 35.05万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Gq-coupled Receptors Inhibit PI 3-kinase/Akt Signaling Pathway
Gq 偶联受体抑制 PI 3 激酶/Akt 信号通路
- 批准号:
8003647 - 财政年份:2009
- 资助金额:
$ 35.05万 - 项目类别:
Molecular Therapy Targeting PTEN-Akt Signaling Pathway in Prostate Cancer.
前列腺癌中针对 PTEN-Akt 信号通路的分子治疗。
- 批准号:
17591697 - 财政年份:2005
- 资助金额:
$ 35.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Gq-coupled Receptors Inhibit PI 3-kinase/Akt Signaling Pathway
Gq 偶联受体抑制 PI 3 激酶/Akt 信号通路
- 批准号:
7525551 - 财政年份:2002
- 资助金额:
$ 35.05万 - 项目类别:
Gq-coupled Receptors Inhibit PI 3-kinase/Akt Signaling Pathway
Gq 偶联受体抑制 PI 3 激酶/Akt 信号通路
- 批准号:
7645586 - 财政年份:2002
- 资助金额:
$ 35.05万 - 项目类别:
Gq-Coupled Receptors Inhibit PI 3-Kinase/Akt Signaling Pathway
Gq 偶联受体抑制 PI 3 激酶/Akt 信号通路
- 批准号:
8064263 - 财政年份:2002
- 资助金额:
$ 35.05万 - 项目类别:
Gq-Coupled Receptors Inhibit PI 3-Kinase/Akt Signaling Pathway
Gq 偶联受体抑制 PI 3 激酶/Akt 信号通路
- 批准号:
8274809 - 财政年份:2002
- 资助金额:
$ 35.05万 - 项目类别: