GRK2 overexpression inhibits IGF1-induced proliferation and migration of human hepatocellular carcinoma cells by downregulating EGR1

Ma,Yang; Han,Chen-Chen; Huang,Qiong; Sun,Wu-Yi; Wei,Wei

doi:10.3892/or.2016.4641

GRK2 overexpression inhibits IGF1-induced proliferation and migration of human hepatocellular carcinoma cells by downregulating EGR1

Authors:
- Yang Ma
- Chen-Chen Han
- Qiong Huang
- Wu-Yi Sun
- Wei Wei
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Affiliations: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, Anhui 230032, P.R. China
Published online on: February 26, 2016 https://doi.org/10.3892/or.2016.4641
Pages: 3068-3074

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Abstract

G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase that is involved in a variety of important signaling pathways and alternation of GRK2 protein level or activity causes diseases such as heart failure, rheumatoid arthritis, and obesity. However, the role and mechanism of GRK2 in hepatocellular carcinoma (HCC) progression is not fully investigated. In this study we found that GRK2 plays an inhibitory role in IGF1-induced HCC cell proliferation and migration. Overexpression of GRK2 causes a decrease in early growth response-1 (EGR1) expression, while knockdown of GRK2 leads to marked increase in EGR1 expression in the treatment of IGF1. Through co-immunoprecipitation and western blot assay, we confirmed that GRK2 can interact with insulin-like growth factor 1 receptor (IGF-1R) and inhibits IGF1-induced activation of IGF1R signaling pathway. Silencing EGR1 attenuates GRK2 overexpression-caused inhibition of cell proliferation, tumor colony number and migration activity, while overexpressing of EGR1 restores the anti-proliferative and migratory effect by GRK2 overexpression in HCCLM3 cells. Collectively, these results suggest that GRK2 may inhibit IGF1-induced HCC cell growth and migration through downregulation of EGR1 and indicate that enforced GRK2 may offer a potential therapeutic approach against HCC.

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