Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling
Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling
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DOI：
10.1101/gad.1668708
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发表时间：
2008-08-01
影响因子：
10.5
通讯作者：
Kim, Hyunggee
中科院分区：
文献类型：
--
作者：
Jeon, Hye-Min;Jin, Xun;Kim, Hyunggee
细胞起源和控制胶质母细胞瘤（GBM）发生和维持的遗传因素尚不清楚。在这里，我们报道了发育调节剂Id4（分化抑制剂4）在GBM中的发病作用。在小鼠Ink4a/Arf(-/)-星形胶质细胞和人类胶质瘤细胞中，我们提供的证据表明，Id4可以通过刺激cyclin E的增加产生超增殖特征，以及通过增加Jagged1的表达和Notch1的激活来驱动星形胶质细胞进入神经干细胞样细胞状态，从而驱动恶性转化。因此，Id4在星形胶质细胞的转化过程中，通过双关键细胞周期和分化调节分子的联合作用发挥着不可或缺的作用。
Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf(-/)-astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.