The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway.
Molecules
; 25(24)2020 Dec 19.
Article
em En
| MEDLINE
| ID: mdl-33352739
ABSTRACT
Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids-dexamethasone and prednisone-did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. We showed that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pregnenodionas
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Fatores de Transcrição
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Células-Tronco Neoplásicas
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Neoplasias da Mama
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Transdução de Sinais
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Receptores de Glucocorticoides
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Antiasmáticos
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Proteínas Adaptadoras de Transdução de Sinal
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article