PLAGL2 通过调节 Wnt 信号通路抑制神经干细胞和神经胶质瘤的分化。
PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.
机构信息
Belfer Institute for Applied Cancer Science, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2010 May 18;17(5):497-509. doi: 10.1016/j.ccr.2010.03.020.
A hallmark feature of glioblastoma is its strong self-renewal potential and immature differentiation state, which contributes to its plasticity and therapeutic resistance. Here, integrated genomic and biological analyses identified PLAGL2 as a potent protooncogene targeted for amplification/gain in malignant gliomas. Enhanced PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell differentiation while promoting their self-renewal capacity upon differentiation induction. Transcriptome analysis revealed that these differentiation-suppressive activities are attributable in part to PLAGL2 modulation of Wnt/beta-catenin signaling. Inhibition of Wnt signaling partially restores PLAGL2-expressing NSC differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics in malignant cells.
胶质母细胞瘤的一个显著特征是其强大的自我更新能力和不成熟的分化状态，这有助于其可塑性和治疗抵抗。在这里，综合基因组和生物学分析鉴定 PLAGL2 为一种潜在的原癌基因，在恶性神经胶质瘤中被靶向扩增/获得。增强的 PLAGL2 表达强烈抑制神经干细胞（NSC）和神经胶质瘤起始细胞的分化，同时在分化诱导时促进其自我更新能力。转录组分析表明，这些分化抑制活性部分归因于 PLAGL2 对 Wnt/β-catenin 信号的调节。Wnt 信号的抑制部分恢复了表达 PLAGL2 的 NSC 的分化能力。PLAGL2 作为神经胶质瘤癌基因的鉴定突出了一类不断增长的癌症基因的重要性，这些基因在恶性细胞中赋予了类似干细胞的特征。
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