Abstract

Glioma stem cells (GSCs) are a subset of tumor cells that drive glioma initiation and progression. The molecular mechanisms underlying the maintenance of GSCs are still poorly understood. Here we investigated the role of Rho GDP dissociation inhibitor α (RhoGDIα) in GSCs. RhoGDIα was down-regulated in glioma stem cells. Over-expression of RhoGDIα suppressed the self-renewal and tumorigenesis of GSCs. Further data showed that RhoGDIα inhibited the transcription activity of stem cell marker Oct4. Moreover, inactivation of ROCK1, a downstream effector of RhoGDIα, also decreased the self-renewal and Oct4 transcription activity, and rescued the effects caused by RhoGDIα knockdown. Our results indicate that RhoGDIα is involved in the maintenance of GSCs.

Highlights

  • Glioma is the most common and lethal primary brain tumor with few advances in treatment

  • Since Rho GDP dissociation inhibitor α (RhoGDIα) is critical to Glioma stem cells (GSCs) self-renewal capacity, we examined whether ectopic expression of RhoGDIα impacts the tumorigenicity of GSCs

  • To confirm RhoA/Rho-associated protein kinase1 (ROCK1) as a critical molecular mediating the effects of RhoGDIα on self-renewal, we examined whether ROCK1 inhibition could rescue the effects caused by RhoGDIα knockdown

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Summary

Introduction

Glioma is the most common and lethal primary brain tumor with few advances in treatment. Despite of current standard therapy, the life expectancy of patients with glioblastma (GBM) is about 14 months [1]. Increasing evidences revealed that glioma contains a minor of cells referred to as glioma stem cells(GSCs), which are characterized by their self-renewal potential and strong tumorigenic capacity [2,3,4]. GSCs have been shown to be more resistant to conventional chemotherapy and radiotherapy, and responsible for glioma recurrence [5,6,7]. A novel therapeutic strategy that directly targets and eradicates GSCs was proposed. The understanding of the biology of GSCs remains partial, and the regulation mechanism of stemness maintenance and tumorigenesis needs further study

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