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Profilin as a target to suppress Invasive breast cancer

Profilin 作为抑制侵袭性乳腺癌的靶点

基本信息

批准号：
9481886
负责人：
PARTHA ROY
金额：
$ 4.65万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-12 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9481886
关键词：
1-Phosphatidylinositol 3-Kinase Actin-Binding Protein Actins Adenocarcinoma Affect Animals Behavior Binding Binding Proteins Biological Assay Breast Cancer Cell Breast Cancer Patient Breast cancer metastasis Cells Cessation of life Clinical Cytoskeletal Proteins Cytoskeleton Cytosol Down-Regulation Family Fluorescence Fluorescence Resonance Energy Transfer Funding Future Goals Histopathology In Vitro Knowledge Lead Link Malignant - descriptor Malignant Neoplasms Mammary Neoplasms Mammary gland Mediating Membrane Molecular Mus Neoplasm Metastasis Oncogenes Outcome Pathway interactions Patients Phosphatidylinositols Physiological Play Prognostic Marker Proteins Proto-Oncogene Proteins c-akt Recruitment Activity Regulation Research Retrospective cohort Role Signal Transduction Spectrum Analysis Study models Testing Therapeutic Time Tumor Cell Biology United States Up-Regulation Woman arm cancer imaging cell motility gain of function genetic regulatory protein in vivo insight intravital imaging live cell imaging malignant breast neoplasm mouse model neoplastic cell novel phosphoinositide-3,4,5-triphosphate phosphoinositide-3,4-bisphosphate polymerization predict clinical outcome profilin profilin 1 tumor tumor progression vasodilator-stimulated phosphoprotein

项目摘要

DESCRIPTION (provided by applicant): The overall goal of the proposed project is to investigate the functional significance of profilin-1 (Pfn1 - a cytoskeleton regulatory protein) downregulation in breast cancer. We will study how Pfn1, a traditionally pro- migratory molecule, can also regulate intracellular signaling generated at the membrane-cytosol interface to suppress breast cancer invasion and metastasis. In Aim 1, we will first combine clinical correlation and mouse model studies to determine whether a) there is a casual relationship between Pfn1 dysregulation and metastatic progression of breast cancer, and b) Pfn1 expression reflects stages in tumor progression and predicts clinical outcome of breast cancer patients (Aim 1). In Aims 2 and 3, we will identify the molecular pathways by which Pfn1 inhibits breast cancer dissemination Successful completion of these studies will determine whether Pfn1 could be used as a prognostic marker in breast cancer and justify novel cancer therapeutics revolving around Pfn1.

描述（由申请人提供）：拟议项目的总体目标是研究profin -1 （Pfn1 -一种细胞骨架调节蛋白）下调在乳腺癌中的功能意义。我们将研究Pfn1，一个传统的亲迁移分子，如何调节在膜-细胞质界面产生的细胞内信号传导，从而抑制乳腺癌的侵袭和转移。在Aim 1中，我们将首先结合临床相关性和小鼠模型研究来确定a) Pfn1异常与乳腺癌转移进展之间是否存在因果关系，b) Pfn1表达反映肿瘤进展阶段并预测乳腺癌患者的临床结局（Aim 1）。在目标2和目标3中，我们将确定Pfn1抑制乳腺癌传播的分子途径。这些研究的成功完成将决定Pfn1是否可以作为乳腺癌的预后标志物，并证明围绕Pfn1的新型癌症治疗方法是合理的。