DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma.
Cancer Lett
; 459: 135-144, 2019 09 10.
Article
em En
| MEDLINE
| ID: mdl-31176743
ABSTRACT
DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a highly conserved kinase whose hyperactivation is critically involved in a variety of human tumors. The role of DEPTOR playing in pituitary adenoma (PA) is largely unknown. Here, we reported that DEPTOR was downregulated in PA tissues, especially dopamine-resistant prolactinomas. Consistently, overexpression of DEPTOR inhibited pituitary tumor GH3 and MMQ cells proliferation in vitro and in vivo, and sensitized GH3 and MMQ cells to cabergoline (CAB), a dopamine agonist (DA). Conversely, knockdown of DEPTOR promoted GH3 and MMQ cells proliferation, and conferred cells resistance to CAB. Mechanistically, DEPTOR inhibited both mTOR Complex 1 (mTORC1) and 2 (mTORC2) activities in PA cells. In addition, DEPTOR expression level was increased to suppress mTOR kinase activity via decreasing E3 ubiquitin ligase, ßTrCP1, in response to CAB. Furthermore, DEPTOR enhanced autophagy-dependent cell death to confer cells sensitivity to CAB. Taken together, our results suggest that DEPTOR may be a potential target for the treatment of PAs.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Hipofisárias
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Adenoma
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Agonistas de Dopamina
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Peptídeos e Proteínas de Sinalização Intracelular
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article