<i>SOX2</i> Silencing in Glioblastoma Tumor-Initiating Cells Causes Stop of Proliferation and Loss of Tumorigenicity

TLDR

Glioblastoma is the most aggressive cerebral tumor and invariably lethal, with tumor cells expressing neural stem cell genes such as the master regulator SOX2 that sustains self‑renewal. The study aimed to determine whether SOX2 drives glioblastoma growth by silencing it in tumor‑initiating cells. SOX2 was silenced in freshly derived glioblastoma tumor‑initiating cells to assess its effect on proliferation and tumorigenicity. Silencing SOX2 halted proliferation and eliminated tumorigenicity of glioblastoma TICs, indicating SOX2 is essential for self‑renewal and a promising therapeutic target.

Abstract

Abstract Glioblastoma, the most aggressive cerebral tumor, is invariably lethal. Glioblastoma cells express several genes typical of normal neural stem cells. One of them, SOX2, is a master gene involved in sustaining self-renewal of several stem cells, in particular neural stem cells. To investigate its role in the aberrant growth of glioblastoma, we silenced SOX2 in freshly derived glioblastoma tumor-initiating cells (TICs). Our results indicate that SOX2 silenced glioblastoma TICs, despite the many mutations they have accumulated, stop proliferating and lose tumorigenicity in immunodeficient mice. SOX2 is then also fundamental for maintenance of the self-renewal capacity of neural stem cells when they have acquired cancer properties. SOX2, or its immediate downstream effectors, would then be an ideal target for glioblastoma therapy.