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Filamin A is required for somatostatin receptor type 5 expression and pasireotide-mediated signaling in pituitary corticotroph tumor cells.
- Source :
-
Molecular and cellular endocrinology [Mol Cell Endocrinol] 2021 Mar 15; Vol. 524, pp. 111159. Date of Electronic Publication: 2021 Jan 09. - Publication Year :
- 2021
-
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.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Apoptosis
Cell Line, Tumor
Cell Proliferation
Gene Silencing
Hormones metabolism
Humans
Mice
Protein Binding
Somatostatin metabolism
Corticotrophs metabolism
Filamins metabolism
Pituitary Neoplasms metabolism
Receptors, Somatostatin metabolism
Signal Transduction
Somatostatin analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8057
- Volume :
- 524
- Database :
- MEDLINE
- Journal :
- Molecular and cellular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 33428965
- Full Text :
- https://doi.org/10.1016/j.mce.2021.111159