A Novel β2-AR/YB-1/β-catenin Axis Mediates Chronic Stress-associated Metastasis in Hepatocellular Carcinoma

Overview

Journal Oncogenesis

Date 2020 Sep 25

PMID 32973139

Citations 19

Authors

Jinxia Liu

Lishuai Qu

Chunhua Wan

Mingbing Xiao

Wenkai Ni

Feng Jiang

Yihui Fan

Cuihua Lu

Runzhou Ni

Affiliations

Soon will be listed here.

Abstract

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 significantly correlated with YB-1, which favours the progression of HCC. The binding of YB-1 with β2-AR resulted in YB-1 phosphorylation at serine 102 (S102) via the β-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. β2-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 β-catenin as a crucial target of YB-1. Our results unveiled a novel β2-AR-mediated regulatory axis in HCC metastasis that might be helpful for the development of HCC therapeutics.

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