GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway.
Xiaoting YuJing JinYanwen ZhengHua ZhuHui XuJun MaQing LanZhixiang ZhuangClark C ChenMing LiPublished in: Cell death & disease (2021)
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.
Keyphrases
- induced apoptosis
- signaling pathway
- cell proliferation
- end stage renal disease
- cell cycle arrest
- poor prognosis
- randomized controlled trial
- stem cells
- tyrosine kinase
- pi k akt
- chronic kidney disease
- ejection fraction
- newly diagnosed
- magnetic resonance
- peritoneal dialysis
- bone marrow
- cell death
- endoplasmic reticulum stress
- prognostic factors
- skeletal muscle
- adipose tissue
- binding protein
- insulin resistance
- cancer therapy
- patient reported outcomes
- nucleic acid