Adrenergic Blockade Promotes Maintenance of Dormancy in Prostate Cancer Through Upregulation of GAS6.

ABSTRACT: Men diagnosed with localized prostate cancer can develop metastases many years after initial treatment, resulting in a poor prognosis. The purpose of this study was to investigate the mechanisms by which signaling through norepinephrine (NE) may incite relapse of quiescent prostate cancer. We used an unbiased bioinformatics pipeline to examine mechanisms for recurrence related to sympathetic signaling in the bone marrow. A transcription factor cell array identified ATF1, RAR, and E2F as key nodes in prostate cancer cells exiting quiescence through adrenergic signaling. Subsequent secretome analysis identified GAS6 as affecting activity of these three factors, leading to cell cycle reentry. GAS6 expression was downregulated in osteoblasts through activation of the cAMP pathway and was targe

SUBMITTER: Decker AM 

PROVIDER: S-EPMC7191848 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature