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Aspects of Cadherin/Catenin Complexes

钙粘蛋白/连环蛋白复合物的方面

基本信息

批准号：
7666737
负责人：
KEITH R JOHNSON
金额：
$ 35.68万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7666737
关键词：
Actins Adhesions Adhesives Attenuated Behavior Breast Cancer Cell Cadherins Cancer Biology Cancer cell line Cell physiology Cell-Cell Adhesion Cell-Matrix Junction Cells Cellular biology Characteristics Complex Data Diagnosis Endothelial Cells Epithelial Cells Family Fibroblast Growth Factor Receptors Funding Grant Guanosine Triphosphate Phosphohydrolases Health Human Intercellular Junctions Investigation Laboratories Link Maintenance Malignant - descriptor Mammary gland Mediating Mesenchymal Methods N-Cadherin Pathway interactions Phosphorylation Platelet-Derived Growth Factor Platelet-Derived Growth Factor Receptor Play Proteins RNA Interference Research Research Personnel Role Signal Pathway Signal Transduction Structure Testing Tube Tumor Cell Biology alpha catenin angiogenesis base beta catenin cadherin 5 cell behavior cell motility dimer epithelial to mesenchymal transition in vivo Model interest knock-down malignant breast neoplasm matrigel member migration neoplastic cell novel programs receptor response rho stem tumor tumor progression tumorigenesis vasodilator-stimulated phosphoprotein

项目摘要

DESCRIPTION (provided by applicant): This is a competing renewal of a project focused on understanding the role of the cadherin/catenin complex in modulating cellular behavior that is relevant to tumorigenesis. In this grant period, we will expand our investigations into the mechanisms whereby cadherin complexes influence cell behavior by exploring crosstalk between cell-cell and cell-matrix interactions, since both types of adhesion are critical to cellular processes like migration and invasion. In particular, our studies will focus on how one member of the cadherin/catenin complex, Alpha-catenin, coordinates cell-cell adhesion with activity of invadopodia, a cell substrate adhesive structure that mediates invasion in tumor cells. Our overall hypothesis is that alpha-catenin plays a central role in coordinating cellular signals that regulate cell-cell and cell-matrix adhesion through its interactions with actin cytoskeletal components and signaling pathways. This hypothesis stems from strong preliminary evidence generated using an alpha-catenin-null human breast cancer cell line that undergoes remodeling of invadopodia in response to alpha-catenin re- expression. Our specific aims are: 1) to determine if alpha-catenin interacts directly with components of invadopodia; 2) to test the hypotheses that VASP function is important for maintenance of invadopodia and that expression of beta-catenin modulates VASP function; and 3) to define the role of alpha-catenin in regulating ERK signaling. Tumor formation and invasion are significant human health problems. The proposed research focuses on understanding how a cell coordinates changes in cell-cell and cell-matrix interactions as it becomes malignant. A basic understanding of tumor cell biology and the mechanisms involved in tumorigenesis will provide a basis for developing new methods for diagnosis and treatment. Studies proposed here will increase our understanding of cancer biology by identifying pathways involved in the cross talk between cell- cell and cell-matrix interactions and by characterizing signaling roles for beta-catenin, which is an understudied component of cellular junctions.

描述（由申请人提供）：这是一个项目的竞争性更新，重点是了解钙粘蛋白/连环蛋白复合物在调节与肿瘤发生相关的细胞行为中的作用。在此资助期内，我们将通过探索细胞-细胞和细胞-基质相互作用之间的串扰来扩展我们对钙粘蛋白复合物影响细胞行为的机制的研究，因为这两种类型的粘附对细胞迁移和入侵等过程至关重要。特别是，我们的研究将集中在钙粘蛋白/连环蛋白复合体的一个成员，α -连环蛋白，如何协调细胞-细胞粘附与invadopodia（一种介导肿瘤细胞侵袭的细胞底物粘附结构）的活性。我们的总体假设是，α -连环蛋白通过与肌动蛋白细胞骨架成分和信号通路的相互作用，在协调细胞信号中发挥核心作用，调节细胞-细胞和细胞-基质的粘附。这一假设源于强有力的初步证据，该证据是利用一种缺乏α -catenin的人乳腺癌细胞系产生的，该细胞系在α -catenin再表达的反应中经历了侵过足的重塑。我们的具体目标是：1)确定α -连环蛋白是否直接与侵adopodia的成分相互作用；2)验证VASP功能对侵过足维持的重要作用和β -连环蛋白的表达调节VASP功能的假设；3)确定α -catenin在调节ERK信号传导中的作用。肿瘤的形成和侵袭是人类重大的健康问题。提出的研究重点是了解细胞如何在细胞-细胞和细胞-基质相互作用中协调变化，因为它变成恶性的。对肿瘤细胞生物学和肿瘤发生机制的基本了解将为开发新的诊断和治疗方法提供基础。这里提出的研究将通过识别细胞-细胞和细胞-基质相互作用之间的串扰通路以及通过表征β -连环蛋白的信号作用来增加我们对癌症生物学的理解，β -连环蛋白是细胞连接的一个未被充分研究的成分。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Expression artifact with retroviral vectors based on pBMN.

基于 pBMN 的逆转录病毒载体的表达产物。

DOI：
10.1016/j.ab.2009.07.014
发表时间：
2009
期刊：
Analytical biochemistry
影响因子：
2.9
作者：
Fukunaga,Yoshitaka;Svoboda,RobertA;Cerny,RonaldL;Johnson,KeithR;Wheelock,MargaretJ
通讯作者：
Wheelock,MargaretJ

N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression.