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

• Applicant: Professor Dr. Robert Grosse
• Subject Area: Pharmacology ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531759725

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.

• DFG Programme: Research Grants