Roles of formins in breast cancer invasion

 描述(由申请人提供)：透明的Forin蛋白家族对肌动蛋白细丝的成核、线性伸长和捆绑非常重要，并在Rho家族的p21小GTP酶下游工作。福尔马林和相关蛋白在乳腺癌的侵袭和转移过程中的作用尚不清楚，特别是与RhoGTPase亚型RhoA和RhoC下游的特异性有关。在这里，我们将为透明的福尔马林家族开发新的荧光生物传感器，该传感器与这一重要的运动调节途径有关，有助于对癌细胞侵袭过程中的分子和细胞分析。目前在更好地了解由Forins控制的分子调控途径方面的局限性，包括控制和协调运动机制(包括肌动蛋白细胞骨架重组、突起和侵入性基质降解)的透明相关Forins(DRF)，这是由于缺乏先进的成像技术能够专门针对活细胞中的这些重要信号节点。我们将把这些新的生物传感器与我们已证实的Rho GTP酶生物传感器结合使用，直接探索这些哺乳动物透明形成蛋白mDia1和mDia2亚型在转移性乳腺癌侵袭过程中调节肿瘤侵袭的机制。

 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.