Spaderna S, Schmalhofer O, Hlubek F, Jung A, Kirchner T, Brabletz T
Dept. of Visceral Surgery, Universityhospital Freiburg.
Verh Dtsch Ges Pathol. 2007;91:21-8.
Invasion by colorectal carcinomas is characterized by an epithelial-mesenchymal transition (EMT)-like de-differentiation of the tumor cells. However a re-differentiation towards an epithelial phenotype, resembling a mesenchymal-epithelial transition (MET) is detectable in metastases. This indicates that malignant progression is based on dynamic processes, which can not 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 beta-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 beta-catenin, which is reversed in metastases. Nuclear beta-catenin is involved in two fundamental processes in embryonic development: EMT and stem cell formation. Accumulating data demonstrate that aberrant nuclear expression of beta-catenin can confere these two abilites also to tumor cells. The unusual combination of EMT with stem cell competence might result in a migrating tumor stem cell, which drives tumor invasion and metastasis.
结直肠癌的侵袭特征是肿瘤细胞发生类似上皮-间质转化（EMT）的去分化。然而，在转移灶中可检测到肿瘤细胞向类似间质-上皮转化（MET）的上皮表型重新分化。这表明恶性进展基于动态过程，不能仅用不可逆的基因改变来解释，还必须由肿瘤微环境进行额外调控。结直肠癌中的主要癌蛋白是Wnt信号通路效应因子β-连环蛋白，在大多数情况下，由于APC肿瘤抑制基因的突变，其表达会上调。肿瘤细胞的EMT与转录激活因子β-连环蛋白的核内积累有关，而在转移灶中这种积累会逆转。核内β-连环蛋白参与胚胎发育中的两个基本过程：EMT和干细胞形成。越来越多的数据表明，β-连环蛋白异常的核表达也可赋予肿瘤细胞这两种能力。EMT与干细胞能力的异常结合可能产生迁移性肿瘤干细胞，驱动肿瘤侵袭和转移。
