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PROX1 promotes human glioblastoma cell proliferation and invasion via activation of the nuclear factor-κB signaling pathway

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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 factorκB (NFκB) 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 vectortransfected controls. Furthermore, ectopic expression of PROX1 promoted the growth of GBM xenograft tumors. Western blot analysis revealed that PROX1 overexpression induced nuclear accumulation of NFκB p65 and upregulated the expression levels of the NFκB responsive genes cyclin D1 and matrix metallopeptidase¬†9. An NFκB reporter assay demonstrated that PROX1overexpressing glioblastoma cells had significantly greater NFκBdependent reporter activities compared with empty vectortransfected controls. Transfection of a dominant inhibitor of κBα mutant into PROX1overexpressing cells significantly impaired their proliferation and invasion capacities, which was accompanied by reduced levels of nuclear NFκB p65. Collectively, these data indicated that PROX1 serves an oncogenic role in GBM and promotes cell proliferation and invasiveness potentially via activation of the NFκB signaling pathway. Therefore, PROX1 may represent a potential target for the treatment of GBM.
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Document Type: Research Article

Affiliations: 1: Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian, Henan 463000, P.R. China 2: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China

Publication date: January 1, 2017

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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