PDE5A and neoplasm: Moreover, BRAF V600E seems to be also implicated in tumor dissemination and invasion by (i) activating the GTPase Rho protein that causes reorganization of the cytoskeleton; (ii) downregulating phosphodiesterase 5A (PDE5A) with increase of cGMP levels; (iii) enhancing cortactin and Exo70 phosphorylation mediated by ERK, with consequent actin cytoskeleton reorganization and metalloproteinases exocytosis (Figure 2).