Wnt/FZD signaling and colorectal cancer morphogenesis
Wnt/FZD signaling and colorectal cancer morphogenesis
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DOI：
10.2741/2075
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发表时间：
2007-01-01
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影响因子：
--
通讯作者：
Brabletz, Thomas
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文献类型：
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作者：
Hlubek, Falk;Spaderna, Simone;Brabletz, Thomas
结直肠癌的恶性进展以侵袭性肿瘤细胞的上皮-间充质转化(EMT)样去分化为特征。然而，在转移瘤中可以检测到向上皮表型的再分化，类似于间充质-上皮转变(MET)。这表明恶性进展是基于动态过程的，这不能仅仅用不可逆转的基因改变来解释，而必须另外受到肿瘤环境的调节。结直肠癌中的主要癌蛋白是Wnt途径效应蛋白β-catenin，在大多数情况下，由于腺瘤性息肉病(APC)抑癌基因的突变，该蛋白过表达。肿瘤细胞的EMT与转录激活剂β-连环蛋白的核积聚有关，而在转移瘤中则相反。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，β-连环蛋白的异常核表达也可以赋予肿瘤细胞这两种能力，表明异常的Wnt信号在恶性肿瘤进展中起着至关重要的作用。
Malignant progression of colorectal carcinomas is characterized by an epithelial-mesenchymal transition (EMT)-like de-differentiation of the invading 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 in most cases is overexpressed due to mutations in the adenomatous polyposis coli (APC) tumor suppressor. EMT of 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 also confer these two abilities to tumor cells, indicating the crucial role of aberrant Wnt-signaling for malignant tumor progression.