Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (−43±21%, P<0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (−46±18%, P<0.05 vs untreated cells), P-ERK1/2 levels (−42±14%; P<0.05 vs untreated cells), cAMP accumulation (−24±3%, P<0.05 vs untreated cells), VEGF expression (−31±5%, P<0.01 vs untreated cells) and in vitro release (−40±24%, P<0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (+86±45%, P<0.05 vs untreated cells) and inhibited cell migration (−24±2%, P<0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients.
Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association
