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

 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（由申请人提供）：Rho蛋白的透明家族对于肌动蛋白丝的成核和线性延伸以及成束是重要的，并且在Rho家族的p21小GTP酶的下游起作用。formins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，特别是与RhoGT β亚型RhoA与RhoC的下游特异性有关。在这里，我们将开发新的荧光生物传感器的透明家庭的formins相关的这一重要的运动调节途径，用于分子和细胞分析的癌细胞在入侵。目前的限制，以更好地了解由formin控制的分子调控途径，包括透明相关formin（DRF），控制和协调的运动机制，包括肌动蛋白细胞骨架重组，突起，和侵入性基质降解，是由于缺乏先进的成像技术，能够特异性地针对这些重要的信号节点在活细胞。我们将使用这些新的生物传感器与我们已证实的Rho GTP酶生物传感器相结合，直接探测这些哺乳动物透明细胞mDia1和mDia2亚型在转移性乳腺腺癌的侵袭伪足突起中癌症侵袭过程中的调节机制。

项目成果

Macropinosome formation by tent pole ruffling in macrophages.

• DOI: 10.1083/jcb.201804137
• 发表时间: 2018-11-05
• 期刊: The Journal of cell biology
• 作者: Condon ND;Heddleston JM;Chew TL;Luo L;McPherson PS;Ioannou MS;Hodgson L;Stow JL;Wall AA
• 通讯作者: Wall AA

Asymmetric localization of DLC1 defines avian trunk neural crest polarity for directional delamination and migration.

• DOI: 10.1038/s41467-017-01107-0
• 发表时间: 2017-10-30
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Liu JA;Rao Y;Cheung MPL;Hui MN;Wu MH;Chan LK;Ng IO;Niu B;Cheah KSE;Sharma R;Hodgson L;Cheung M
• 通讯作者: Cheung M