期刊
ONCOGENESIS
卷 9, 期 9, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41389-020-00268-w
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资金
- National Natural Science Foundation of China [81401985, 81472272, 8167238]
- Jiangsu Government Scholarship for Overseas Studies [JS-2018-122]
- Six Talent Peaks Project in Jiangsu Province [WSN-057]
- Jiangsu Provincial Natural Science Foundation [BK20161286]
- Postdoctoral Science Foundation of China [2017M620221, 2020M670039ZX]
- Social Development Foundation of Nantong City [MS32018010, MS12017002-6]
beta-Adrenergic receptor (beta-AR) signalling is strongly associated with tumour progression by the coupling of beta-ARs with either a G protein or beta-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 beta 2-adrenergic receptor (beta 2-AR) following stimulation with the agonist isoproterenol (ISO). Clinicopathological analysis demonstrated that beta 2-AR is significantly correlated with YB-1, which favours the progression of HCC. The binding of YB-1 with beta 2-AR resulted in YB-1 phosphorylation at serine 102 (S102) via the beta-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. beta 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 beta-catenin as a crucial target of YB-1. Our results unveiled a novel beta 2-AR-mediated regulatory axis in HCC metastasis that might be helpful for the development of HCC therapeutics.
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