Formin-mediated secretion of Angiopoietin-like 4 for cancer cell invasion

福尔明介导的血管生成素样 4 分泌促进癌细胞侵袭

• 批准号: 531759725
• 负责人: Professor Dr. Robert Grosse
• 金额: --
• 依托单位: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/531759725?language=en
• 关键词: Formin; mediated; secretion; Angiopoietin; like

Vesicle trafficking has emerged as an important process driving tumor progression through various mechanisms. TGFβ-mediated secretion of ANGPTL4 is important for cancer development such as breast cancer. Here, we will investigate the role of the actin nucleator Formin-like 2 (FMNL2) for ANGPTL4 trafficking and secretion in response to TGFβ. We will study phosphorylation of FMNL2 downstream of TGFβ stimulation for ANGPTL4 vesicle trafficking, secretion and cancer cell invasion. Moreover, using super resolution microscopy, we will analyse how ANGPTL4 trafficking is actin-dependent and how FMNL2 promotes actin polymerisation at ANGPTL4-containing vesicles for intracellular movement. Our work shall elucidate how a formin-controlled mechanism that transiently polymerizes actin directly at intracellular vesicles facilitates their secretion to drive TGFβ-mediated tumor cell invasion and thus identify novel pharmacological targets and principles.

囊泡运输已成为通过各种机制推动肿瘤进展的重要过程。TGFβ介导的ANGPTL4分泌对于癌症发展如乳腺癌是重要的。在这里，我们将研究肌动蛋白成核剂Formin样2（FMNL 2）在响应TGFβ的ANGPTL 4运输和分泌中的作用。我们将研究TGFβ刺激下游FMNL 2的磷酸化对ANGPTL 4囊泡运输、分泌和癌细胞侵袭的影响。此外，使用超分辨率显微镜，我们将分析ANGPTL4的运输是如何肌动蛋白依赖性和FMNL 2如何促进肌动蛋白聚合在ANGPTL4含有囊泡的细胞内运动。我们的工作将阐明一个formin控制的机制，瞬时聚合肌动蛋白直接在细胞内囊泡促进其分泌，以驱动TGFβ介导的肿瘤细胞侵袭，从而确定新的药理学目标和原则。