Invasion and metastasis in colorectal cancer:: Epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and β-catenin
Invasion and metastasis in colorectal cancer:: Epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and β-catenin
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DOI：
10.1159/000084509
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发表时间：
2005-01-01
影响因子：
2.7
通讯作者：
Kirchner, T
中科院分区：
文献类型：
--
作者：
Brabletz, T;Hlubek, F;Kirchner, T
结直肠癌侵袭的特征是肿瘤细胞的上皮-间质转化（EMT）样去分化。然而，向上皮表型的再分化，类似于间充质上皮转化，在转移中可以检测到。这表明恶性进展是基于动态过程的，不能仅仅通过不可逆的遗传改变来解释，而必须受到肿瘤环境的额外调节。结直肠癌的主要癌蛋白是Wnt通路效应蛋白β-catenin，在大多数情况下，由于APC抑癌基因突变导致其过表达。肿瘤细胞的EMT与转录激活因子β-连环蛋白的核积累有关，这在转移中是逆转的。细胞核β-连环蛋白参与胚胎发育的两个基本过程：EMT和干细胞形成。越来越多的数据表明，细胞核中β-catenin的异常表达也可以赋予肿瘤细胞这两种能力，从而推动恶性肿瘤的进展。版权所有(C) 2005 S. Karger AG，巴塞尔。
Invasion by colorectal carcinomas is characterized by an epithelial-mesenchymal transition (EMT)-like dedifferentiation of the tumor cells. However, a redifferentiation towards an epithelial phenotype, resembling a mesenchymal-epithelial transition, is detectable in metastases. This indicates that malignant progression is based on dynamic processes, which cannot be explained solely by irreversible genetic alterations, but must be additionally regulated by the tumor environment. The main oncoprotein in colorectal cancer is the Wnt pathway effector β-catenin, which is overexpressed due to mutations in the APC tumor suppressor in most cases. EMT of the tumor cells is associated with a nuclear accumulation of the transcriptional activator β-catenin, which is reversed in metastases. Nuclear β-catenin is involved in two fundamental processes in embryonic development: EMT and stem cell formation. Accumulating data demonstrate that aberrant nuclear expression of β-catenin can also confer these two abilities to tumor cells, thereby driving malignant tumor progression. Copyright (C) 2005 S. Karger AG, Basel.