Filamin A is required for somatostatin receptor type 5 expression and pasireotide-mediated signaling in pituitary corticotroph tumor cells

Donatella Treppiedi, Genesio Di Muro, Federica Mangili, Rosa Catalano, Elena Giardino, Anna Maria Barbieri, Marco Locatelli, Maura Arosio, Anna Spada, Erika Peverelli, Giovanna Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

Somatostatin receptor type 5 (SST5) represents the main pharmacological target in the treatment of adrenocorticotroph hormone (ACTH)-secreting tumors. However, molecular predictors of responsiveness to pasireotide require further investigation. The cytoskeleton protein filamin A (FLNA) modulates the responsiveness to somatostatin analogs (SSA) treatment in other types of pituitary tumors by regulating somatostatin receptor type 2 (SST2)/dopamine receptor type 2 (DRD2) expression and activity. Here, we aimed to test the involvement of FLNA in the modulation of SST5 response to SSA in human and murine tumor corticotrophs. Western blot analysis of human corticotropinomas showed that FLNA and SST5 correlate. Both in human primary cultures and AtT-20 cells, FLNA genetic silencing caused a decrease of receptor expression level. Moreover, pasireotide-mediated SST5 downregulation observed in AtT-20 control cells was no further detected in FLNA silenced cells. In AtT-20 cells, in situ PLA experiments revealed an increased number of SST5-FLNA complexes following pasireotide incubation. Finally, FLNA knock down abolished pasireotide-induced SST5 actions on hormone secretion, cell proliferation and apoptosis. In conclusion, FLNA is implicated in SST5 expression modulation and signaling.

Original languageEnglish
Article number111159
JournalMolecular and Cellular Endocrinology
Volume524
DOIs
Publication statusPublished - Mar 15 2021

Keywords

  • ACTH-secreting pituitary tumors
  • FLNA
  • Pasireotide
  • SST5

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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