GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway

• Published in: Cell death & disease 2021-02, Vol.12 (2), p.203-203, Article 203
• Main Authors: Yu, Xiaoting, Jin, Jing, Zheng, Yanwen, Zhu, Hua, Xu, Hui, Ma, Jun, Lan, Qing, Zhuang, Zhixiang, Chen, Clark C., Li, Ming
• Format: Article
• Language: English
• Subjects: 13/51; 13/95; 42/89; 45/77; 631/67/1922; 631/67/395; 64/60; 82/1; 82/29; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Brain cancer; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain tumors; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Movement; Cell Proliferation; Extracellular signal-regulated kinase; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - enzymology; Glioblastoma - genetics; Glioblastoma - pathology; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Humans; Immunology; Interferon; Life Sciences; Malignancy; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 3 - metabolism; Medical prognosis; Mesenchyme; Mice; Mice, Nude; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Neoplasm Invasiveness; Phosphorylation; RNA-mediated interference; Signal Transduction; src-Family Kinases - metabolism; Tumor Burden
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03492-3

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.