title: PROX1 promotes human glioblastoma cell proliferation and invasion via activation of the nuclear factor-κB signaling pathway.
abstract: Prospero homeobox protein 1 (PROX1) is highly expressed in high-grade malignant astrocytic gliomas. However, the role of PROX1 in the pathogenesis of glioblastoma multiforme (GBM) remains unclear. The present study overexpressed PROX1 in human GBM cell lines and examined its effects on cell growth, tumorigenesis, and invasiveness. In addition, the involvement of the nuclear factor‑κB (NF‑κB) signaling pathway in the action of PROX1 was examined. It was identified that overexpression of PROX1 significantly increased the proliferation and colony formation of glioblastoma cells, compared with empty vector‑transfected controls. Furthermore, ectopic expression of PROX1 promoted the growth of GBM xenograft tumors. Western blot analysis revealed that PROX1 overexpression induced nuclear accumulation of NF‑κB p65 and upregulated the expression levels of the NF‑κB responsive genes cyclin D1 and matrix metallopeptidase 9. An NF‑κB reporter assay demonstrated that PROX1‑overexpressing glioblastoma cells had significantly greater NF‑κB‑dependent reporter activities compared with empty vector‑transfected controls. Transfection of a dominant inhibitor of κBα mutant into PROX1‑overexpressing cells significantly impaired their proliferation and invasion capacities, which was accompanied by reduced levels of nuclear NF‑κB p65. Collectively, these data indicated that PROX1 serves an oncogenic role in GBM and promotes cell proliferation and invasiveness potentially via activation of the NF‑κB signaling pathway. Therefore, PROX1 may represent a potential target for the treatment of GBM.
authors.affiliation: Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian, Henan 463000, P.R. China.
authors.forename: Xuchang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian, Henan 463000, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Xinting
authors.initials: X
authors.lastname: Wei
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000276:immunology*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000276:immunology / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein