Roles of formins in breast cancer invasion

福尔明在乳腺癌侵袭中的作用

• 批准号: 9098870
• 负责人: Louis Hodgson
• 金额: $ 18.16万
• 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/9098870
• 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; Life; Malignant Neoplasms; Mediating; Microfilaments; Molecular; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; Pathway interactions; Phenotype; Phosphotransferases; Process; Protein Isoforms; Protein Tyrosine Kinase; 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.