Cholesterol-activated stress granules reduce the membrane localization of DRD2 and promote prolactinoma dopamine agonists resistance.

ABSTRACT: Prolactinoma is the most prevalent pituitary neuroendocrine tumor and dopamine agonists (DAs) targeting dopamine D2 receptor (DRD2) are recommended as the first-line treatment. However, varying degrees of DA resistance limit patient benefit. Our study used transcriptome sequencing of surgical tumor samples and found abnormal cholesterol metabolism in prolactinoma, especially in DA-resistant tumors. We found that cholesterol significantly enhanced the resistance of prolactinoma MMQ cell lines to cabergoline in vitro and in vivo xenografts. Further, cholesterol did not affect the total protein level of DRD2, but changed the distribution of DRD2 with downregulation of its membrane abundance and upregulation of cytoplasmic localization. Mechanistically, immunoprecipitation combined with mass s

SUBMITTER: Peng Y 

PROVIDER: S-EPMC12023431 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature