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

囊泡运输已成为通过多种机制驱动肿瘤进展的重要过程。tgf β介导的ANGPTL4分泌在乳腺癌等癌症的发展中起重要作用。在这里，我们将研究肌动蛋白核子Formin-like 2 （FMNL2）在响应TGFβ的ANGPTL4运输和分泌中的作用。我们将研究TGFβ刺激下游FMNL2磷酸化对ANGPTL4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运输如何依赖于肌动蛋白，以及FMNL2如何促进含有ANGPTL4的囊泡中的肌动蛋白聚合以进行细胞内运动。我们的工作将阐明一种formin控制的机制，即直接在细胞内囊泡瞬时聚合肌动蛋白，促进其分泌，从而驱动tgf β介导的肿瘤细胞侵袭，从而确定新的药理靶点和原理。

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.