Gebeshuber Christoph A, Sladecek Stefan, Grunert Stefan
Institute for Molecular Pathology Vienna, Vienna, Austria.
Cells Tissues Organs. 2007;185(1-3):51-60. doi: 10.1159/000101303.
Although the role of Wnt signalling in breast cancer is far from being fully understood, in the last years its importance has been reported frequently. Besides stimulation by canonical Wnt signalling, the downstream effectors beta-catenin and the transcriptional modulators of the T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) family can also be activated by other inputs including the TGF-beta pathway. Wnt and TGF-beta signalling are both major signal transduction pathways, which provide important cues during development and tumor progression. However, particularly TGF-beta has a complicated influence on oncogenesis, which ranges from suppressive to promoting activity. Signalling pathways activated in parallel with TGF-beta might determine the oncogenic influence, and therefore place signals cooperating with TGF-beta into the limelight. During early development Wnt and TGF-beta signalling collaborate extensively. Here we provide an overview of the known interactions of Wnt with TGF-beta signalling in development and metastasis, particularly in breast cancer. We want to focus on the Wnt-activated transcription factor complex beta-catenin/LEF-1, its upstream activators, its downstream targets and consequences on the cellular level in response to beta-catenin/LEF-1 activation.
尽管Wnt信号通路在乳腺癌中的作用远未被完全了解，但在过去几年中，其重要性已被频繁报道。除了经典Wnt信号通路的刺激外，下游效应分子β-连环蛋白以及T细胞因子/淋巴样增强子结合因子（TCF/LEF）家族的转录调节因子也可被包括TGF-β通路在内的其他输入激活。Wnt和TGF-β信号通路都是主要的信号转导通路，在发育和肿瘤进展过程中提供重要线索。然而，尤其是TGF-β对肿瘤发生具有复杂的影响，其范围从抑制活性到促进活性。与TGF-β平行激活的信号通路可能决定致癌影响，因此使与TGF-β协同作用的信号备受关注。在早期发育过程中，Wnt和TGF-β信号通路广泛协作。在这里，我们概述了Wnt与TGF-β信号通路在发育和转移过程中，特别是在乳腺癌中的已知相互作用。我们将重点关注Wnt激活的转录因子复合物β-连环蛋白/LEF-1、其上游激活剂、其下游靶点以及β-连环蛋白/LEF-1激活后在细胞水平上的后果。
