@entity146 cells can engage in a process termed vasculogenic mimicry (VM) that reflects the ability of @entity5 cells to express a multipotent, stem cell-like phenotype. @entity320 cell plasticity contributes to the lack of efficient therapeutic strategies targeting @entity3 . This study reveals @entity1919 as a mediator of VM in vitro. In uveal and cutaneous metastatic aggressive @entity1 @entity320 cells, an increase in @entity1919 by @entity1928 , @entity5393 , or @entity2231 ( @entity2231 ) ligands such as adrenaline and vasoactive intestinal peptide inhibited VM to different extents. Although chemical modulators of protein kinase A (PKA) had no effect, a specific pharmacologic activator of Exchange protein directly activated by @entity1919 ( @entity21919 ) impaired VM. @entity56707 ( @entity56707 ) activation assays revealed that @entity1919 -elevating agents induce a PKA-independent activation of @entity21919 / @entity56707 . Pharmacologic inhibition of @entity3962 ( @entity1366 ) activity abolished VM. Phosphorylation of @entity1366 was PKA-independently inhibited by @entity1928 but not inhibited by @entity21919 / @entity56707 signaling, PKA modulation, or @entity2231 ligands. Furthermore, the @entity1928 also inhibited @entity47150 inositol-3-kinase (PI3K)-mediated activation of protein kinase @entity584 , as monitored by Ser473 phosphorylation. The pharmacologic activation of @entity21919 and @entity2231 ligands slightly stimulated @entity584 , a likely concomitant process of VM modulation. Collectively, these data show that @entity1928 strongly inhibits VM through PKA-independent activation of @entity21919 / @entity56707 , PKA-, and @entity21919 -independent inactivation of @entity1366 and inhibition of PI3K/ @entity584 . The data also show that VM inhibition by @entity2231 ligands involves mainly the @entity21919 / @entity56707 -activated signal. Thus @entity1919 inhibits VM through multiple signaling pathways.

@entity1919 signaling as a mediator of vasculogenic mimicry in aggressive @entity1 XXXX cells in vitro.

@entity1 :: ('9606', 'Species') :: ['human'] @entity146 :: ('MESH:D001523', 'Disease') :: ['Aggressive melanoma'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity21919 :: ('10411', 'Gene') :: ['Epac'] @entity3962 :: ('5594;5595', 'Gene') :: ['extracellular signal-regulated kinase 1/2'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity2231 :: ('1909', 'Gene') :: ['GPCR', 'G protein-coupled receptor'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['cyclic AMP'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic tumors'] @entity47150 :: ('CHEBI:26025', 'Chemical') :: ['phosphatidyl'] @entity1366 :: ('5595;5594', 'Gene') :: ['ERK1/2'] @entity56707 :: ('27342', 'Gene') :: ['Ras-associated protein-1', 'Rap1'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'Melanoma'] @entity1928 :: ('MESH:D005576', 'Chemical') :: ['forskolin'] @entity5393 :: ('MESH:D003994', 'Chemical') :: ['dibutyryl cyclic AMP']
@entity320 :: (MESH:D008545,Disease) :: ['melanoma']
