| 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 cancers.However,the role of DEPTOR playing in pituitary adenoma is largely unknown.Here,we reported that DEPTOR was downregulated in pituitary adenoma 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,and induced cell arrest in pituitary adenoma cells.In addition,DEPTOR expression level was increased to suppress mTOR kinase activity in response to CAB via decreasing E3 ubiquitin ligase,βTrCP1.Furthermore,DEPTOR enhanced autophagy-dependent cell death to confer cells sensitivity to CAB.Taken together,our results suggested that DEPTOR may be a promising strategy for the treatment of pituitary adenomas. |
