Coronin-1C (CRN2, coronin-3) dependent migration and invasion of tumor cells

冠状蛋白是一种保守的肌动蛋白结合蛋白，可以促进依赖肌动蛋白细胞骨架重塑的过程。我们研究了普遍表达的CRN 2(冠状病毒-1C，冠状病毒-3)。它定位于哺乳动物细胞的胞浆、片状脂膜和膜褶皱，并直接与F-肌动蛋白结合并捆绑在一起。过表达和敲除研究表明，CRN2是板脂蛋白形成所必需的，并影响细胞迁移和对细胞外基质的侵袭。对人脑肿瘤的分析表明，CRN2与弥漫性胶质瘤的恶性表型有关。本研究的目的是明确CRN_2在肿瘤恶性中的作用，分析CRN_2在肿瘤细胞形成和转移中的分子机制，并确定CRN_2的表达作为判断预后的因素。我们已经建立了一种小鼠模型，用来探讨CRN2在肿瘤进展、侵袭和转移中的作用。我们进一步研究了CRN 2与肌动蛋白细胞骨架相互作用的机制和调控，确定了CRN 2的进一步相互作用，并阐明了这些特征如何有助于CRN 2在癌症进展中的作用。

Coronins are conserved actin-binding proteins that promote processes that rely on a remodelling of the actin cytoskeleton. We study the ubiquitously expressed CRN2 (coronin-1C, coronin-3). It localizes to the cytosol and to lamellipodia and membrane ruffles in mammalian cells and directly binds to and bundles F-actin. Overexpression and knockdown studies indicate that CRN2 is required for the formation of lamellipodia and affects cell migration and invasion into extracellular matrix. Analysis of human brain tumors showed that CRN2 is associated with the malignant phenotype of diffuse gliomas. Goal of this project is to define the contribution of CRN2 to tumor malignancy, to analyse the molecular mechanisms of CRN2 in tumor cell formation and metastasis and to determine CRN2 expression as a factor for prognosis. We have established a mouse model with which we probe the contribution of CRN2 to tumor progression, invasion and metastasis. We further study the mechanism and regulation of CRN2 interaction with the actin cytoskeleton, identify further interactions of CRN2 and elucidate how these features contribute to the role of CRN2 in cancer progression.