Ludwig Institute for Cancer Research, Uppsala University, Box 595, 75124, Uppsala, Sweden.
Breast Cancer Res. 2012 Feb 8;14(1):204. doi: 10.1186/bcr3066.
Smad proteins are the key intermediates of transforming growth factor-beta (TGF-β) signaling during development and in tissue homeostasis. Pertubations in TGF-β/Smad signaling have been implicated in cancer and other diseases. In the cell nucleus, Smad complexes trigger cell type- and context-specific transcriptional programs, thereby transmitting and integrating signals from a variety of ligands of the TGF-β superfamily and other stimuli in the cell microenvironment. The actual transcriptional and biological outcome of Smad activation critically depends on the genomic integrity and the modification state of genome and chromatin of the cell. The cytoplasmic and nuclear Smads can also modulate the activity of other signal transducers and enzymes such as microRNA-processing factors. In the case of breast cancer, the role of Smads in epithelial plasticity, tumor-stroma interactions, invasion, and metastasis seems of particular importance.
Smad 蛋白是转化生长因子-β（TGF-β）信号通路在发育和组织稳态中的关键中间产物。TGF-β/Smad 信号通路的紊乱与癌症和其他疾病有关。在细胞核内，Smad 复合物触发细胞类型和上下文特异性转录程序，从而传递和整合来自 TGF-β 超家族的各种配体和细胞微环境中的其他刺激物的信号。Smad 激活的实际转录和生物学结果严重依赖于细胞基因组的完整性和染色质的修饰状态。细胞质和核内 Smad 还可以调节其他信号转导物和酶的活性，如 microRNA 加工因子。在乳腺癌中，Smads 在上皮可塑性、肿瘤-基质相互作用、侵袭和转移中的作用似乎尤为重要。
