The Role of Cripto in the Pathogenesis of Breast and Col

Cripto 在乳腺和结肠发病机制中的作用

基本信息

  • 批准号:
    6762087
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep ), mouse cripto (Cr-1) and cryptic and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the embryonic anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right asymmetry. In the mouse cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of a human CR-1 transgene in the mouse mammary gland using an MMTV promoter results in the appearance of ductal hyperplasias in the mammary gland and papillary adenocarcinomas in multiparous female mice. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mouse mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta-catenin adherens function and an increase in vimentin expression. Expression of CR-1 is increased several-fold in human colon, gastric, pancreatic, cervical, ovarian and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase in cripto-1 expression can first be detected in premalignant lesions in some of these tissues such as in the breast ( hyperplasias and DCIS ), colon ( adenomas ) and stomach ( intestinal metaplasias ). We have recently identied the Activin ALK4 type 1 receptor as a co-receptor for CR-1 which presents Nodal to ALK4 and thereby can stimulate Smad-2 phosphorylation and transcription through an SBE-luciferase reporter construct.In addition, CR-1 can function through a Nodal and ALK4-independent signaling pathway and activate MAPK, PI-3 kinase and Akt by binding to the GPI-linked heparan sulphate-containing proteoglycan, glypican-1 which can then activate c-src. Activation of MAPK, PI-3 kinase, GSK-3beta and Akt in mammary epithelial cells by CR-1 are required for the ability of CR-1 to stimulate cell proliferation, transformation in vitro, cell migration and to block lactogenic hormone-induced expression of beta-casein and whey acidic protein. In mammary epithelial cells part of these responses may also depend on the ability of CR-1 by activating c-src through glypican-1 the tyrosine transphosphorylation of the erbB-4 and/or FGFR-1 receptors.
EGF-cfc基因家族编码一组结构上相关的蛋白质,在非洲爪哇、斑马鱼、小鼠和人类的早期胚胎发育过程中,这些蛋白质是重要的竞争因子。这个多基因家族由非洲爪哇FRL-1、斑马鱼独眼针头(OEP)、小鼠Cripto(CR-1)、隐形和人类Cripto(CR-1)和criptin组成。FRL-1、OEP和小鼠CRIPTO对于中胚层和内胚层的形成以及胚胎前/后轴的正确建立是必不可少的。此外,OEP和CRYPTIC对于左右不对称的建立也很重要。在小鼠中,CR1在成年组织中不表达,而在包括乳腺在内的几个不同组织中低水平表达。在乳腺中,在妊娠和哺乳期间,乳腺导管上皮细胞中铬-1的表达增加,在人乳中可以检测到具有免疫活性和生物活性的铬-1蛋白。使用MMTV启动子在小鼠乳腺中过表达人CR-1转基因会导致乳腺导管增生和经产雌性小鼠乳头状腺癌的出现。重组小鼠或人CRIPTO可增强小鼠乳腺上皮细胞和某些人肿瘤细胞的细胞运动能力和分支形态发生。这些效应伴随着上皮向间充质的转变,这与β-连环蛋白黏附功能的降低和波形蛋白表达的增加有关。CR-1在人类结肠癌、胃癌、胰腺癌、宫颈癌、卵巢癌和肺癌以及各种不同类型的小鼠和人乳腺癌中的表达增加了几倍。更重要的是,Cripto-1表达的增加首先可以在癌前病变中检测到,这些组织中的一些组织,如乳腺(增生症和DCIS)、结肠(腺瘤)和胃 (肠化生)。我们最近发现激活素ALK41型受体是CR-1的共同受体,它向ALK4递送Nodal,从而通过构建SBE-荧光素酶报告结构来刺激Smad-2的磷酸化和转录。此外,CR-1可以通过Nodal和ALK4不依赖的信号通路发挥作用,并通过与GPI连接的含有硫酸乙酰肝素的蛋白多糖Glypcan-1激活MAPK、PI-3激酶和Akt,从而激活c-src。CR-1对乳腺上皮细胞MAPK、PI-3、GSK-3β和Akt的激活是CR-1刺激细胞增殖、体外转化、细胞迁移和阻断乳源激素诱导的β-酪蛋白和乳清酸性蛋白表达所必需的。在乳腺上皮细胞中,这些反应的一部分也可能依赖于CR-1的能力,它通过GLIPICAN-1激活c-src,即erbB-4和/或FGFR-1受体的酪氨酸转磷酸化。

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 }}

DAVID SALOMON其他文献

DAVID SALOMON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('DAVID SALOMON', 18)}}的其他基金

The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    7732932
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Col
Cripto 在乳腺和结肠发病机制中的作用
  • 批准号:
    7292123
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    6433130
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    7965131
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    8348915
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
THE ROLE OF EGF-RELATED PEPTIDES IN THE PATHOGENESIS OF BREAST AND COLON CANCER
EGF 相关肽在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    6289225
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Col
Cripto 在乳腺和结肠发病机制中的作用
  • 批准号:
    7338127
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    8552609
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    7592590
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Role of Cripto in the Pathogenesis of Breast and Colon Cancer
Cripto 在乳腺癌和结肠癌发病机制中的作用
  • 批准号:
    8157216
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

相似海外基金

Paracrine and autocrine IL-6 as drivers of treatment resistance in medulloblastoma
旁分泌和自分泌 IL-6 作为髓母细胞瘤治疗抵抗的驱动因素
  • 批准号:
    468060
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Operating Grants
Targeting Autocrine Hepatocyte Growth Factor (HGF) Production as a Therapeutic Modality in Acute Myeloid Leukemia (AML)
靶向自分泌肝细胞生长因子 (HGF) 的产生作为急性髓系白血病 (AML) 的治疗方式
  • 批准号:
    10589002
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Autocrine and paracrine podocyte signals decrease glomerular function/health in aged kidneys
自分泌和旁分泌足细胞信号会降低老年肾脏的肾小球功能/健康
  • 批准号:
    10698100
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Elucidating the role of autocrine TNF signaling in maintaining human regulatory T cell identity
阐明自分泌 TNF 信号传导在维持人类调节性 T 细胞身份中的作用
  • 批准号:
    BB/W001055/1
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Autocrine Action of Elevated FGF-21 Contributing to Skeletal Muscle Atrophy in Response to Mitochondrial Dysfunction
FGF-21 升高的自分泌作用导致线粒体功能障碍引起的骨骼肌萎缩
  • 批准号:
    10615236
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
Rôle autocrine des exosomes sécrétés par le muscle dans un contexte de diabète de type 2
2 型糖尿病背景下肌肉中外泌体的自分泌作用
  • 批准号:
    466812
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
    Studentship Programs
Autocrine Action of Elevated FGF-21 Contributing to Skeletal Muscle Atrophy in Response to Mitochondrial Dysfunction
FGF-21 升高的自分泌作用导致线粒体功能障碍引起的骨骼肌萎缩
  • 批准号:
    10296083
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
Autocrine Action of Elevated FGF-21 Contributing to Skeletal Muscle Atrophy in Response to Mitochondrial Dysfunction
FGF-21 升高的自分泌作用导致线粒体功能障碍引起的骨骼肌萎缩
  • 批准号:
    10469480
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
Mitochondrial reactive oxygen species act as autocrine neuromodulators in retinal ganglion cells
线粒体活性氧在视网膜神经节细胞中充当自分泌神经调节剂
  • 批准号:
    10157645
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
Mitochondrial reactive oxygen species act as autocrine neuromodulators in retinal ganglion cells
线粒体活性氧在视网膜神经节细胞中充当自分泌神经调节剂
  • 批准号:
    10343744
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了