GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway
Open Access
- 19 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 12 (2), 1-11
- https://doi.org/10.1038/s41419-021-03492-3
Abstract
Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.Keywords
This publication has 33 references indexed in Scilit:
- Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expressionCancer Letters, 2013
- Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastomaThe Journal of Experimental Medicine, 2011
- Identification of Guanylate-Binding Protein 1 as a Potential Oral Cancer Marker Involved in Cell Invasion Using Omics-Based AnalysisJournal of Proteome Research, 2011
- The Guanylate-Binding Proteins: Emerging Insights into the Biochemical Properties and Functions of This Family of Large Interferon-Induced Guanosine TriphosphataseJournal of Interferon & Cytokine Research, 2011
- Importance of Protein-tyrosine Phosphatase-α Catalytic Domains for Interactions with SHP-2 and Interleukin-1-induced Matrix Metalloproteinase-3 ExpressionOnline Journal of Public Health Informatics, 2010
- Matrix Metalloproteinases As Novel Biomarker s and Potential Therapeutic Targets in Human CancerJournal of Clinical Oncology, 2009
- Malignant astrocytic glioma: genetics, biology, and paths to treatmentGenes & Development, 2007
- Unique Features of Different Members of the Human Guanylate-Binding Protein FamilyJournal of Interferon & Cytokine Research, 2007
- The dynamin superfamily: universal membrane tubulation and fission molecules?Nature Reviews Molecular Cell Biology, 2004
- Extracellular matrix degradation by metalloproteinases and central nervous system diseasesMolecular Neurobiology, 1999