Vesicle-Associated Actin Assembly by Formins Promotes TGFβ-Induced ANGPTL4 Trafficking, Secretion and Cell Invasion.
Vesicle trafficking has emerged as an important process driving tumor progression through various mechanisms. Transforming growth factor beta (TGFβ)-mediated secretion of Angiopoietin-like 4 (ANGPTL4) is important for cancer development. Here, Formin-like 2 (FMNL2) is identified to be necessary for ANGPTL4 trafficking and secretion in response to TGFβ. Protein kinase C (PKC)-dependent phosphorylation of FMNL2 downstream of TGFβ stimulation is required for cancer cell invasion as well as ANGPTL4 vesicle trafficking and secretion. Moreover, using super resolution microscopy, ANGPTL4 trafficking is actin-dependent with FMNL2 directly polymerizing actin at ANGPTL4-containing vesicles, which are associated with Rab8a and myosin Vb. This work uncovers a formin-controlled mechanism that transiently polymerizes actin directly at intracellular vesicles to facilitate their mobility. This mechanism may be important for the regulation of cancer cell metastasis and tumor progression.