Abstract
Simple SummaryGlioblastoma is the most common and lethal primary brain tumor for which no curative treatment currently exists. In our previous work, we showed that MEOX2 was associated with a poor patient prognosis but its biological involvement in tumor development remains ill defined. To this purpose, the aim of our study was to investigate the role of MEOX2 in patient-derived glioblastoma cell cultures. We unraveled the MEOX2 contribution to cell viability and growth and its potential involvement in phenotype and adhesion properties of glioblastoma cells. This work paves the way toward a better understanding of the role of MEOX2 in the pathophysiology of primary brain tumors.The high expression of MEOX2 transcription factor is closely associated with poor overall survival in glioma. MEOX2 has recently been described as an interesting prognostic biomarker, especially for lower grade glioma. MEOX2 has never been studied in glioma stem-like cells (GSC), responsible for glioma recurrence. The aim of our study was to investigate the role of MEOX2 in GSC. Loss of function approach using siRNA was used to assess the impact of MEOX2 on GSC viability and stemness phenotype. MEOX2 was localized in the nucleus and its expression was heterogeneous between GSCs. MEOX2 expression depends on the methylation state of its promoter and is strongly associated with IDH mutations. MEOX2 is involved in cell proliferation and viability regulation through ERK/MAPK and PI3K/AKT pathways. MEOX2 loss of function correlated with GSC differentiation and acquisition of neuronal lineage characteristics. Besides, inhibition of MEOX2 is correlated with increased expression of CDH10 and decreased pFAK. In this study, we unraveled, for the first time, MEOX2 contribution to cell viability and proliferation through AKT/ERK pathway and its potential involvement in phenotype and adhesion properties of GSC.
Highlights
Glioma stem-like cells (GSC) is a subpopulation of cells present in the tumor with characteristics similar to the neural progenitor cells [1,2]
These results suggested that the expression of MEOX2 was nuclear and heterogeneous in glioma stem-like cells (GSC)
These results show that MEOX2 has antiproliferative effect in GSC by the modulation of ERK/MAPK and PI3K/AKT pathways
Summary
Glioma stem-like cells (GSC) is a subpopulation of cells present in the tumor with characteristics similar to the neural progenitor cells [1,2]. GSC present fundamental stem characteristics consisting of self-renewal, multipotency, and high tumorigenicity [3,4]. These cells can survive exogenous DNA damage such as radiation-induced double strand breaks or chemotherapeutic drugs and repopulate the tumor following treatment, thereby contributing to radiotherapy resistance, chemoresistance and tumor recurrence [5,6]. Growing evidence suggests that transcription factors play a major role in maintaining the stem or differentiating properties of cells [7]. One study identified 19 transcription factors, involved in neurodevelopment and selectively expressed in GSC, which maintained stemness phenotype and prevented differentiation [8]. Homeobox genes, encoding transcription factors, have been described as major player of stem property regulation during embryonic development and in cancers [9]
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