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.

Highlights

  • Gliomas, the most common and lethal primary intracranial tumors in adults, originate from de-differentiated glial cells or glial-like precursors[1]

  • guanylate binding protein 5 (GBP5) is upregulated in GBM tumors and cell lines and predicts poor outcomes

  • The results showed that the adjacent normal brain tissues expressed low levels of GBP5, while 14 of 20 (70%) tumor samples expressed higher levels (Fig. 1A)

Read more

Summary

Introduction

The most common and lethal primary intracranial tumors in adults, originate from de-differentiated glial cells or glial-like precursors[1]. Glioblastoma (GBM) is the most aggressive subtype of glioma, accounting for more than half of all astrocytoma cases, which has been categorized as a World Health Organization grade IV glioma. GBM is a heterogeneous tumor characterized by angiogenesis, proliferation, invasion, and evasion of apoptosis. Recurrence rate of GBM remains as high as 90%. Patients with GBM have a median overall survival of 15–18 months with treatment, and the 5-year survival is

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.