Roles of formins in breast cancer invasion

福尔明在乳腺癌侵袭中的作用

• 批准号: 9254499
• 负责人: Louis Hodgson
• 金额: $ 21.79万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-06 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9254499
• 关键词: Actins; Address; Affect; Area; Biological Models; Biosensor; Breast Adenocarcinoma; Bundling; Cells; Cytoskeleton; Development; Extracellular Matrix; Extracellular Matrix Degradation; Family; Genetic; Guanosine Triphosphate Phosphohydrolases; Homologous Protein; Imaging technology; Integrins; Malignant Neoplasms; Mediating; Microfilaments; Molecular; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; Pathway interactions; Phenotype; Phosphotransferases; Process; Protein Isoforms; Proteins; Recruitment Activity; Regulation; Regulatory Pathway; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Specificity; Structure; Subcellular structure; Time; cancer cell; cancer invasiveness; cell motility; density; malignant breast neoplasm; new technology; public health relevance; rho; rho GTP-Binding Proteins; tool; tumor; Actins; Address; Affect; Area; Biological Models; Biosensor; Breast Adenocarcinoma; Bundling; Cells; Cytoskeleton; Development; Extracellular Matrix; Extracellular Matrix Degradation; Family; Genetic; Guanosine Triphosphate Phosphohydrolases; Homologous Protein; Imaging technology; Integrins; Malignant Neoplasms; Mediating; Microfilaments; Molecular; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; Pathway interactions; Phenotype; Phosphotransferases; Process; Protein Isoforms; Proteins; Recruitment Activity; Regulation; Regulatory Pathway; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Specificity; Structure; Subcellular structure; Time; cancer cell; cancer invasiveness; cell motility; density; malignant breast neoplasm; new technology; public health relevance; rho; rho GTP-Binding Proteins; tool; tumor

 DESCRIPTION (provided by applicant): Diaphanous family of formin protein is important for nucleation and linear elongation and bundling of actin filaments, and operate downstream of p21 small GTPases of the Rho family. The roles of formins and related proteins during motility and invasion process of breast cancers are not clearly known, especially in relation to the downstream specificity of the RhoGTPase isoforms RhoA versus RhoC. Here, we will develop new fluorescent biosensors for Diaphanous family of formins pertinent to this important motility regulatory pathway, useful for molecular and cellular analysis of cancer cells during invasion. The current limitations to better understanding the molecular regulatory pathways controlled by formins including the Diaphanous related formins (DRF) that control and coordinate the motile mechanisms including actin cytoskeleton reorganization, protrusions, and invasive matrix degradation, are due to lack of sophisticated imaging technologies capable of specifically targeting these important signaling nodes in living cells. We will use these new biosensors in combination with our proven biosensors for the Rho GTPases to directly probe the mechanisms these mammalian Diaphanous formin mDia1 and mDia2 isoforms regulate during cancer invasion in invadopodia protrusions of metastatic mammary adenocarcinomas.

 描述（由适用提供）：diaphanous formin蛋白家族对于肌动蛋白丝的成核和线性伸长和束很重要，以及在Rho家族的P21小GTPase下游操作。造型和相关蛋白在乳腺癌的运动和侵袭过程中的作用尚不清楚，尤其是与Rhogtpase同工型RhoA相对于RHOC的下游特异性而言。在这里，我们将开发新的荧光生物传感器，用于与这种重要运动调节途径相关的拟光造型家族，可用于侵袭过程中癌细胞的分子和细胞分析。当前的局限性，以更好地了解由造型控制的分子调节途径，包括diaphanous相关的formins（DRF），这些拟合造型（DRF）控制和协调包括肌动蛋白细胞骨架重组，突起和侵入性基质降解的母体机制，这是由于缺乏精致的成像技术而导致这些具有特殊靶向这些重要信号的nive nive nive nodes nodes nodesnodes nododes nododes nododes nododes nodods node nodss node n of。我们将使用这些新的生物传感器与我们对Rho GTPase的经过验证的生物传感器联合探测这些机制这些机制，这些哺乳动物的驱动式形式甲素MDIA1和MDIA2同工型在癌症侵袭期间在转移性乳腺癌腺癌的癌症中受到癌症侵袭期间受到癌症的调节。