Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters.
Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters.
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DOI：
10.1186/1471-2407-11-49
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发表时间：
2011-02-01
期刊：
影响因子：
3.8
通讯作者：
Zhou BP
中科院分区：
文献类型：
--
作者：
Li J;Zhou BP
上皮-间质转化（Epithelial-mesenchymal transition，EMT）不仅使肿瘤细胞具有明显的转移优势，而且使其具有肿瘤干细胞样的增殖和耐药特性。然而，维持这些干细胞样性状的分子机制仍不清楚。在这项研究中，我们诱导乳腺癌MCF 7和宫颈癌Hela细胞中的EMT与Twist的表达，EMT的关键转录因子。免疫荧光染色和Western blotting分析EMT相关的形态学变化。与EMT相关的干细胞样特征通过这些细胞中的肿瘤球形成和ALDH 1和CD 44的表达来确定。通过Western印迹和荧光素酶测定来检查β-连环蛋白和Akt途径的活化。我们发现Twist的表达诱导了与EMT相关的形态学变化。我们还发现，肿瘤干细胞样特征，如肿瘤球形成，ALDH 1和CD 44的表达，在Twist过表达细胞中显著升高。有趣的是，我们发现β-catenin和Akt通路在这些Twist过表达细胞中被激活。β-连环蛋白的激活与CD 44的表达相关。β-连环蛋白表达的敲低和Akt通路的抑制极大地抑制了CD 44的表达。我们的研究结果表明，β-catenin和Akt通路的激活是维持EMT相关干细胞样性状所必需的。
Epithelial-mesenchymal transition (EMT) not only confers tumor cells with a distinct advantage for metastatic dissemination, but also it provides those cells with cancer stem cell-like characters for proliferation and drug resistance. However, the molecular mechanism for maintenance of these stem cell-like traits remains unclear. In this study, we induced EMT in breast cancer MCF7 and cervical cancer Hela cells with expression of Twist, a key transcriptional factor of EMT. The morphological changes associated with EMT were analyzed by immunofluorescent staining and Western blotting. The stem cell-like traits associated with EMT were determined by tumorsphere-formation and expression of ALDH1 and CD44 in these cells. The activation of β-catenin and Akt pathways was examined by Western blotting and luciferase assays. We found that expression of Twist induced a morphological change associated with EMT. We also found that the cancer stem cell-like traits, such as tumorsphere formation, expression of ALDH1 and CD44, were significantly elevated in Twist-overexpressing cells. Interestingly, we showed that β-catenin and Akt pathways were activated in these Twist-overexpressing cells. Activation of β-catenin correlated with the expression of CD44. Knockdown of β-catenin expression and inhibition of the Akt pathway greatly suppressed the expression of CD44. Our results indicate that activation of β-catenin and Akt pathways are required for the sustention of EMT-associated stem cell-like traits.
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CD44+ CD24（ - ）前列腺细胞是早期的癌症祖/干细胞，为预后不良的患者提供了模型。
影响因子：
8.8
作者：
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作者：
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影响因子：
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作者：
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