GBP2 enhances glioblastoma invasion through Stat3/fibronectin pathway
- 2 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 39 (27), 5042-5055
- https://doi.org/10.1038/s41388-020-1348-7
Abstract
Guanylate-binding protein 2 (GBP2) is an interferon-inducible large GTPase which is crucial to the protective immunity against microorganisms. However, its biological function in cancer remains largely unknown. Glioblastoma multiforme (GBM) is the most common and deadly brain tumor in adults. Here we show that GBP2 expression is highly elevated in GBM tumor and cell lines, particularly in those of the mesenchymal subtype. High GBP2 expression is associated with poor prognosis. GBP2 overexpression significantly promotes GBM cell migration and invasion in vitro, and GBP2 silencing by RNA interference exhibits opposite effects. We further show that fibronectin (FN1) is dramatically induced by GBP2 expression at both mRNA and protein levels, and FN1 is essential for GBP2-promoted GBM invasiveness. Inhibition of Stat3 pathway prevents GBP2-promoted FN1 induction and cell invasion. Consistently, GBP2 dramatically promotes GBM tumor growth and invasion in mice and significantly reduces the survival time of the mice with tumor. Taken together, these findings establish the role of GBP2/Stat3/FN1 signaling cascade in GBM invasion and suggest GBP2 may serve as a potential therapeutic target for inhibiting GBM invasion.Funding Information
- National Natural Science Foundation of China (81572480)
This publication has 34 references indexed in Scilit:
- The landscape of the mesenchymal signature in brain tumoursBrain, 2019
- Interferon-induced guanylate-binding proteins: Guardians of host defense in health and diseaseThe Journal of Experimental Medicine, 2019
- The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summaryActa Neuropathologica, 2016
- STAT3 Blockade Inhibits Radiation-Induced Malignant Progression in GliomaCancer Research, 2015
- The Somatic Genomic Landscape of GlioblastomaCell, 2013
- Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1Cancer Cell, 2010
- The transcriptional network for mesenchymal transformation of brain tumoursNature, 2009
- Guanylate binding protein‐1 inhibits spreading and migration of endothelial cells through induction of integrin α4expressionThe FASEB Journal, 2008
- In SilicoGenomic Analysis of the Human and Murine Guanylate-Binding Protein (GBP) Gene ClustersJournal of Interferon & Cytokine Research, 2006
- The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokinesThe EMBO Journal, 2001