Insulin-Like Growth Factor Binding Protein-2 Promotes Proliferation and Predicts Poor Prognosis in Hepatocellular Carcinoma
| Autor: | Dongqian Cui, Yang Ma, Chen-Chen Han, Yu Zhang, Wei Wei |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway biology business.industry Cell growth Growth factor medicine.medical_treatment EGR1 medicine.disease digestive system diseases Insulin-like growth factor-binding protein Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology ELK1 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research medicine biology.protein Pharmacology (medical) business |
| Zdroj: | OncoTargets and Therapy. 13:5083-5092 |
| ISSN: | 1178-6930 |
| DOI: | 10.2147/ott.s249527 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |