Oncogenic activity of SOX1 in glioblastoma.
Oncogenic activity of SOX1 in glioblastoma.
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DOI：
10.1038/srep46575
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发表时间：
2017-04-20
影响因子：
4.6
通讯作者：
Matheu A
中科院分区：
文献类型：
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作者：
Garcia I;Aldaregia J;Marjanovic Vicentic J;Aldaz P;Moreno-Cugnon L;Torres-Bayona S;Carrasco-Garcia E;Garros-Regulez L;Egaña L;Rubio A;Pollard S;Stevanovic M;Sampron N;Matheu A
胶质母细胞瘤仍然是最常见和最致命的脑肿瘤类型，它含有大量自我更新的、高度致瘤性的胶质瘤干细胞(GSCs)，这些干细胞有助于肿瘤的启动和治疗耐药。参与组织发育和动态平衡的发育程序在GSCs中重新出现，支持胶质母细胞瘤的发展和进展。SOX1在神经发育和神经祖细胞库的维持中起着重要作用。它对胶质母细胞瘤的影响在很大程度上仍不清楚。在这项研究中，我们发现，在部分患者中观察到高水平的SOX1与较低的总存活率相关。在细胞水平上，SOX1的表达在患者来源的GSCs中升高，与传统的胶质母细胞瘤细胞系的分化条件相比，在六钩吻合体培养中也更高。此外，SOX1在患者来源的GSCs和常规细胞系中的遗传抑制会降低体外的自我更新和增殖能力以及体内肿瘤的起始和生长。相反，SOX1的过度表达适度促进了GSC的自我更新和增殖。这些功能似乎不依赖于其作为Wnt/β-catenin信号调节因子的活性。综上所述，这些结果确定了SOX1在调节胶质瘤细胞异质性和可塑性方面的功能作用，并提示SOX1是胶质母细胞瘤GSC群体中的一个潜在靶点。
Glioblastoma remains the most common and deadliest type of brain tumor and contains a population of self-renewing, highly tumorigenic glioma stem cells (GSCs), which contributes to tumor initiation and treatment resistance. Developmental programs participating in tissue development and homeostasis re-emerge in GSCs, supporting the development and progression of glioblastoma. SOX1 plays an important role in neural development and neural progenitor pool maintenance. Its impact on glioblastoma remains largely unknown. In this study, we have found that high levels of SOX1 observed in a subset of patients correlate with lower overall survival. At the cellular level, SOX1 expression is elevated in patient-derived GSCs and it is also higher in oncosphere culture compared to differentiation conditions in conventional glioblastoma cell lines. Moreover, genetic inhibition of SOX1 in patient-derived GSCs and conventional cell lines decreases self-renewal and proliferative capacity in vitro and tumor initiation and growth in vivo. Contrarily, SOX1 over-expression moderately promotes self-renewal and proliferation in GSCs. These functions seem to be independent of its activity as Wnt/β-catenin signaling regulator. In summary, these results identify a functional role for SOX1 in regulating glioma cell heterogeneity and plasticity, and suggest SOX1 as a potential target in the GSC population in glioblastoma.