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A novel ?2-AR/YB-1/?-catenin axis mediates chronic stress-associated metastasis in hepatocellular carcinoma.


ABSTRACT: ?-Adrenergic receptor (?-AR) signalling is strongly associated with tumour progression by the coupling of ?-ARs with either a G protein or ?-arrestin; however, the related mechanism underlying hepatocellular carcinoma (HCC) metastasis is not clear. Here, we reveal that the transcription factor Y-box binding protein 1 (YB-1) interacts with ?2-adrenergic receptor (?2-AR) following stimulation with the agonist isoproterenol (ISO). Clinicopathological analysis demonstrated that ?2-AR is significantly correlated with YB-1, which favours the progression of HCC. The binding of YB-1 with ?2-AR resulted in YB-1 phosphorylation at serine 102 (S102) via the ?-arrestin-1-dependent activation of the PI3K/AKT pathway, followed by the translocation of YB-1 to the nucleus to carry out its tumour-related function. ?2-AR-mediated activation of YB-1 facilitated epithelial-to-mesenchymal transition (EMT) and HCC metastasis. The interference of YB-1 expression significantly attenuated liver tumour metastasis induced by chronic stress. Analysis of the transcriptional profile and chromatin immunoprecipitation (ChIP) identified ?-catenin as a crucial target of YB-1. Our results unveiled a novel ?2-AR-mediated regulatory axis in HCC metastasis that might be helpful for the development of HCC therapeutics.

SUBMITTER: Liu J 

PROVIDER: S-EPMC7515897 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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A novel β2-AR/YB-1/β-catenin axis mediates chronic stress-associated metastasis in hepatocellular carcinoma.

Liu Jinxia J   Qu Lishuai L   Wan Chunhua C   Xiao Mingbing M   Ni Wenkai W   Jiang Feng F   Fan Yihui Y   Lu Cuihua C   Ni Runzhou R  

Oncogenesis 20200924 9


β-Adrenergic receptor (β-AR) signalling is strongly associated with tumour progression by the coupling of β-ARs with either a G protein or β-arrestin; however, the related mechanism underlying hepatocellular carcinoma (HCC) metastasis is not clear. Here, we reveal that the transcription factor Y-box binding protein 1 (YB-1) interacts with β2-adrenergic receptor (β2-AR) following stimulation with the agonist isoproterenol (ISO). Clinicopathological analysis demonstrated that β2-AR is significantl  ...[more]

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