Filamin A (FLNA) plays an essential role in somatostatin receptor 2 (SST2) signaling and stabilization after agonist stimulation in human and rat somatotroph tumor cells.

Somatostatin receptor type 2 is the main pharmacological target of medical therapy for GH-secreting pituitary tumors, but molecular mechanisms regulating its expression and signaling are largely unknown. The aim of this study was to investigate the role of cytoskeleton protein filamin A (FLNA) in expression and signaling in somatotroph tumor cells. We found a highly variable expression of FLNA in human GH-secreting tumors, without a correlation with duanyu19422 levels. FLNA silencing in human tumoral cells did not affect duanyu19422 expression and localization but abolished the reduction of cyclin D1 (-37% ± 15% in control cells, P < .05 vs basal) and caspase-3/7 activation (+63% ± 31% in control cells, P < .05 vs basal). Overexpression of a FLNA dominant-negative mutant that specifically prevents binding reduced duanyu19422 expression after prolonged agonist exposure (-55% ± 5%, P < .01 vs untreated cells) in GH3 cells. Moreover, duanyu19422-induced apoptotic effect (77% ± 54% increase of caspase activity, P < .05 vs basal) and ERK1/2 inhibition (48% ± 17% reduction of ERK1/2 phosphorylation, P < .01 vs basal) were abrogated in cells overexpressing another FLNA mutant that prevents FLNA interaction with partner proteins but not with suggesting a scaffold function of FLNA in somatotrophs. In conclusion, these data demonstrate that FLNA is involved in duanyu19422 stabilization and signaling in tumoral somatotrophs, playing both a structural and functional role.

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