FGF1 signaling regulates self-renewal of glioblastoma stem cells through activation of aurora a kinase

Chien-Yu Kao, Yi-Chao Hsu, I. Chiu
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Abstract

Glioblastoma (GBM) is a highly malignant brain tumor. The GBM tumor mass contains a unique cell population, GBM stem cells (GBM-SCs), which possess the self-renewal, tumor initiating and tumor progression. FGF1B is the major transcriptional variant of FGF1 in GBM. In our recent study, we demonstrated the FGF1B transcript is up-regulated in self-renewing GBM cells. In order to study GBM-SCs, we developed an approach to isolate GBM-SCs by using FGF1B promoter-driven GFP reporter (F1BGFP). We showed that F1BGFP(+) GBM cells exhibit higher phosphorylation levels of FGFR and AurA than F1BGFP(-) cells, indicating the activation of FGFR and AurA. In this research highlight, we summarized the role of FGF1 signaling and AurA in tumorigenesis. In addition, we also suggested that FGF1-FGFR-AurA cascade regulates GBM-SCs, which may enable development of target-based therapy that act against the GBM-SCs.
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FGF1信号通过激活极光激酶调节胶质母细胞瘤干细胞的自我更新
胶质母细胞瘤是一种高度恶性的脑肿瘤。GBM肿瘤团块包含一种独特的细胞群——GBM干细胞(GBM- scs),它具有自我更新、肿瘤启动和肿瘤进展的能力。FGF1B是GBM中FGF1的主要转录变体。在我们最近的研究中,我们证明了FGF1B转录物在自我更新的GBM细胞中上调。为了研究GBM-SCs,我们开发了一种利用FGF1B启动子驱动的GFP报告基因(F1BGFP)分离GBM-SCs的方法。我们发现F1BGFP(+) GBM细胞比F1BGFP(-)细胞表现出更高的FGFR和AurA磷酸化水平,表明FGFR和AurA被激活。在本研究重点中,我们总结了FGF1信号和AurA在肿瘤发生中的作用。此外,我们还提出FGF1-FGFR-AurA级联调节GBM-SCs,这可能促进针对GBM-SCs的靶向治疗的发展。
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