ISSN: 1837-9664Journal of Cancer
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J Cancer 2021; 12(24):7287-7299. doi:10.7150/jca.59291 This issue Cite
Research Paper
β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
*These authors contributed equally to this work.
Citation:
Li XQ, Peng WT, Shan S, Wu JJ, Li N, Du JJ, Sun JC, Chen TT, Wei W, Sun WY. β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression. J Cancer 2021; 12(24):7287-7299. doi:10.7150/jca.59291. https://www.jcancer.org/v12p7287.htm
Other stylesAbstract
Background: β-arrestin2 and β2-adrenergic receptor (β2-AR) have important roles in malignant tumors, the present study aims to investigate the role of activated β2-AR in hepatic stellate cells (HSCs) during hepatocellular carcinoma (HCC) progression and the regulatory effect of β-arrestin2.
Methods: Immunofluorescence and Western blot were used to detect the expression of β-arrestin2 and β2-AR in HSCs of liver tissues from human HCC samples and diethylnitrosamine (DEN)-induced HCC model mice. We next used β-arrestin2-/- mice to demonstrate the regulatory role of β-arrestin2 in DEN mice. The subsets of T cells were quantified by flow cytometry. MTT and wound healing assay were applied to detect the proliferation and migration of cells. Co-immunoprecipitation assay was used to detect the link of β-arrestin2 and β2-AR in HSCs. Effect of β-arrestin2 overexpression on β2-AR downstream signaling pathway was verified by Western blot. The secretion of CCL2 was detected by ELISA.
Results: The expression of β2-AR was significantly increased, while β-arrestin2 was decreased in HSCs of HCC tissues. And β-arrestin2 deficiency exacerbates DEN-induced HCC accompanied with increased β2-AR expression. The results of flow cytometry showed that the percentage of activated T cells decreased gradually after DEN injection. β-arrestin2 knockout down-regulated the ratio of activated T cells. In vitro, selective activation of β2-AR in HSCs promoted the proliferation and migration of HCC cells. β-arrestin2 overexpression enhanced co-immunoprecipitation of β-arrestin2 and β2-AR in activated HSCs, and decreased its downstream Akt phosphorylation. Akt inhibitor decreased secretion of CCL2 in activated HSCs.
Conclusion: Our study demonstrated that β2-AR activation in HSCs induces the proliferation and migration of HCC cells may be through Akt signaling, and this effect appears to be regulated by β-arrestin2.
Keywords: hepatocellular carcinoma, hepatic stellate cells, tumor microenvironment, β2-adrenergic receptor, β-arrestin2
Citation styles
APA
Li, X.Q., Peng, W.T., Shan, S., Wu, J.J., Li, N., Du, J.J., Sun, J.C., Chen, T.T., Wei, W., Sun, W.Y. (2021). β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression. Journal of Cancer, 12(24), 7287-7299. https://doi.org/10.7150/jca.59291.
ACS
Li, X.Q.; Peng, W.T.; Shan, S.; Wu, J.J.; Li, N.; Du, J.J.; Sun, J.C.; Chen, T.T.; Wei, W.; Sun, W.Y. β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression. J. Cancer 2021, 12 (24), 7287-7299. DOI: 10.7150/jca.59291.
NLM
Li XQ, Peng WT, Shan S, Wu JJ, Li N, Du JJ, Sun JC, Chen TT, Wei W, Sun WY. β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression. J Cancer 2021; 12(24):7287-7299. doi:10.7150/jca.59291. https://www.jcancer.org/v12p7287.htm
CSE
Li XQ, Peng WT, Shan S, Wu JJ, Li N, Du JJ, Sun JC, Chen TT, Wei W, Sun WY. 2021. β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression. J Cancer. 12(24):7287-7299.
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