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Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma

BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP2) levels are significantly increased in the plasma of hepatocellular carcinoma (HCC) patients. However, the correlation between IGFBP2 levels and clinical parameters and the exact role of IGFBP2 in HCC are unclear. In this study, we ide...

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Autores principales: Ma, Yang, Cui, Dongqian, Zhang, Yu, Han, Chen-chen, Wei, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292487/
https://www.ncbi.nlm.nih.gov/pubmed/32606730
http://dx.doi.org/10.2147/OTT.S249527
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author Ma, Yang
Cui, Dongqian
Zhang, Yu
Han, Chen-chen
Wei, Wei
author_facet Ma, Yang
Cui, Dongqian
Zhang, Yu
Han, Chen-chen
Wei, Wei
author_sort Ma, Yang
collection PubMed
description BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP2) levels are significantly increased in the plasma of hepatocellular carcinoma (HCC) patients. However, the correlation between IGFBP2 levels and clinical parameters and the exact role of IGFBP2 in HCC are unclear. In this study, we identified the role and potential molecular mechanisms of IGFBP2 in HCC. MATERIALS AND METHODS: ELISA assays were used to detect plasma IGFBP2 levels in HCC patients and healthy controls, and the correlations with patients’ clinicopathological data were analyzed. The CCK8 assay was used to explore cell proliferation. Luciferase reporter, co-immunoprecipitation, and immunofluorescence assays were used to demonstrate the molecular mechanism of IGFBP2 in HCC. RESULTS: Plasma IGFBP2 levels were determined blindly in 37 HCC patients and 37 matched healthy controls. The mean plasma IGFBP2 concentrations in HCC patients were higher than in healthy controls, and IGFBP2 levels in HCC were positively correlated with the degree of differentiation, tumor size, metastasis, and portal venous invasion. Exogenous IGFBP2 activated integrin β1 and thus induced the combination and colocalization of activated integrin β1 and p-FAK, which promoted the phosphorylation of FAK, Erk, and Elk1, eventually inducing EGR1-mediated proliferation of the HCC cell lines HepG2 and HCCLM3. Meanwhile, neutralization of integrin β1 inhibited IGFBP2-induced FAK, Erk, Elk1, and EGR1 activation. CONCLUSION: Taken together, these results indicated that exogenous IGFBP2 promoted the integrin β1/FAK/Erk/Elk1/EGR1 pathway, which stimulated the proliferation of HCC cells. Plasma IGFBP2 could be a novel prognostic biomarker for HCC patients.
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spelling pubmed-72924872020-06-29 Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma Ma, Yang Cui, Dongqian Zhang, Yu Han, Chen-chen Wei, Wei Onco Targets Ther Original Research BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP2) levels are significantly increased in the plasma of hepatocellular carcinoma (HCC) patients. However, the correlation between IGFBP2 levels and clinical parameters and the exact role of IGFBP2 in HCC are unclear. In this study, we identified the role and potential molecular mechanisms of IGFBP2 in HCC. MATERIALS AND METHODS: ELISA assays were used to detect plasma IGFBP2 levels in HCC patients and healthy controls, and the correlations with patients’ clinicopathological data were analyzed. The CCK8 assay was used to explore cell proliferation. Luciferase reporter, co-immunoprecipitation, and immunofluorescence assays were used to demonstrate the molecular mechanism of IGFBP2 in HCC. RESULTS: Plasma IGFBP2 levels were determined blindly in 37 HCC patients and 37 matched healthy controls. The mean plasma IGFBP2 concentrations in HCC patients were higher than in healthy controls, and IGFBP2 levels in HCC were positively correlated with the degree of differentiation, tumor size, metastasis, and portal venous invasion. Exogenous IGFBP2 activated integrin β1 and thus induced the combination and colocalization of activated integrin β1 and p-FAK, which promoted the phosphorylation of FAK, Erk, and Elk1, eventually inducing EGR1-mediated proliferation of the HCC cell lines HepG2 and HCCLM3. Meanwhile, neutralization of integrin β1 inhibited IGFBP2-induced FAK, Erk, Elk1, and EGR1 activation. CONCLUSION: Taken together, these results indicated that exogenous IGFBP2 promoted the integrin β1/FAK/Erk/Elk1/EGR1 pathway, which stimulated the proliferation of HCC cells. Plasma IGFBP2 could be a novel prognostic biomarker for HCC patients. Dove 2020-06-08 /pmc/articles/PMC7292487/ /pubmed/32606730 http://dx.doi.org/10.2147/OTT.S249527 Text en © 2020 Ma et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ma, Yang
Cui, Dongqian
Zhang, Yu
Han, Chen-chen
Wei, Wei
Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
title Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_full Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_fullStr Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_full_unstemmed Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_short Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_sort insulin-like growth factor binding protein-2 promotes proliferation and predicts poor prognosis in hepatocellular carcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292487/
https://www.ncbi.nlm.nih.gov/pubmed/32606730
http://dx.doi.org/10.2147/OTT.S249527
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