Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis
Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis
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DOI：
10.1038/ncomms5697
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Wu, Kou-Juey
中科院分区：
文献类型：
--
作者：
Chen, Hsiao-Fan;Huang, Chi-Hung;Wu, Kou-Juey
肿瘤诱导的血管生成的控制机制目前尚不清楚。原则上，血管生成可以通过激活现有血管中的内皮细胞或通过肿瘤细胞转分化为内皮细胞来实现。然而，肿瘤细胞是否可以通过先前的上皮-间充质转化并进一步分化为内皮细胞仍然是未知的。在这里，我们表明，Twist 1，一种转录调节因子，诱导和促进癌症转移，过度表达，导致头颈癌（HNC）细胞的内皮分化。Twist 1诱导Jagged 1表达是Twist 1诱导内皮细胞分化的关键。Jagged 1/Notch信号随后激活KLF 4，诱导HNC细胞中的干细胞样特性并赋予它们耐药性。我们的研究结果表明，Twist 1-Jagged 1/KLF 4轴是必不可少的肿瘤细胞转分化为内皮细胞和化疗耐药性收购。
The mechanisms controlling tumour-induced angiogenesis are presently not clear. In principle, angiogenesis can be achieved through the activation of endothelial cells in existing vessels or by transdifferentiation of tumour cells into endothelial cells. However, whether tumour cells can go through a prior epithelial-mesenchymal transition and further differentiate into endothelial cells remains unknown. Here we show that overexpression of Twist1, a transcriptional regulator that induces and promotes cancer metastasis, leads to endothelial differentiation in head and neck cancer (HNC) cells. Induction of Jagged1 expression by Twist1 is essential for Twist1-induced endothelial differentiation. The Jagged1/Notch signalling subsequently activates KLF4, inducing stem-like properties in HNC cells and conferring them with drug resistance. Our results indicate that the Twist1-Jagged1/KLF4 axis is essential both for transdifferentiation of tumour cells into endothelial cells and for chemoresistance acquisition.