Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been\nextensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains\nundetermined, especially in regard to stem cell-related pathways.\nMethods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing\nimmunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and\nRT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN\naxis on lung cancer progression was evaluated by cell migration assay and mice study.\nResults: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including\n72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53,\n51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human\nlung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals\nthan those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and\nupregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed\nelevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential.\nConclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus,\ntherapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer,\nespecially when lung cancer is refractory to conventional treatment due to cancer stem cells.
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