Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism
Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism
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DOI：
10.1038/sj.onc.1209712
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发表时间：
2006-11-01
期刊：
影响因子：
8
通讯作者：
Song, J.
中科院分区：
文献类型：
--
作者：
Yang, Y.;Pan, X.;Song, J.
细胞凋亡和上皮细胞向间质细胞转化（EMT）与多种生物学过程有关，如胚胎发育、纤维化和肿瘤进展。转化生长因子-β（transforminggrowthfactor-beta，TGF-β）可同时诱导上皮细胞的EMT和凋亡反应。然而，这些生物学事件的潜在机制仍然没有得到很好的理解。在本研究中，我们发现，TGF-β 1诱导AML-12细胞凋亡和EMT的细胞周期相关的方式，其中凋亡和EMT发生在G2/M和G1/S期，分别。TGF-β 1诱导的细胞凋亡与caspase在细胞周期不同阶段的不同程度的激活有关。有趣的是，在G1/S期可以观察到TGF-β 1对蛋白激酶D（PKD）磷酸化的增加，并且通过抑制剂或小干扰RNA抑制PKD可以阻断EMT，但不能阻断凋亡。我们的数据表明，以前未认识到的作用，细胞周期状态的调节TGF-β诱导的EMT和凋亡，并证明PKD参与TGF-β 1诱导的EMT。
Apoptosis and epithelial-to-mesenchymal transition (EMT) have been implicated in a variety of biological processes, such as embryonic development, fibrosis and tumor progression. Transforming growth factor-beta (TGF-beta) can induce simultaneously both EMT and apoptotic response of epithelial cells. However, the underlying mechanism of these biological events remains not well understood. In the present study, we show that TGF-beta 1 induces apoptosis and EMT in AML-12 cells in a cell cycle-related manner, in which apoptosis and EMT took place at G2/M and G1/S phases, respectively. TGF-beta 1-induced apoptosis was correlated with different extent of caspase activation at different cell cycle phases. Interestingly, increased phosphorylation of protein kinase D (PKD) can be observed in G1/S phase in response to TGF-beta 1, and inhibition of PKD by inhibitor or by small interference RNA blocked EMT but not apoptosis. Our data suggest a previously unrecognized role of cell cycle state in the regulation of TGF-beta-induced EMT and apoptosis, and demonstrate that PKD is involved in the TGF-beta 1-induced EMT.