Department of Cell Biology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Oncogene. 2013 Jul 18;32(29):3397-409. doi: 10.1038/onc.2012.506. Epub 2012 Dec 17.
Development and progression of cancer are mediated by alterations in transcriptional networks, resulting in a disturbed balance between the activity of oncogenes and tumor suppressor genes. Transcription factors have the capacity to regulate global transcriptional profiles, and are consequently often found to be deregulated in their expression and function during tumorigenesis. Sex-determining region Y-related high-mobility-group box transcription factor 4 (SOX4) is a member of the group C subfamily of the SOX transcription factors and has a critical role during embryogenesis, where its expression is widespread and controls the development of numerous tissues. SOX4 expression is elevated in a wide variety of tumors, including leukemia, colorectal cancer, lung cancer and breast cancer, suggesting a fundamental role in the development of these malignancies. In many cancers, deregulated expression of this developmental factor has been correlated with increased cancer cell proliferation, cell survival, inhibition of apoptosis and tumor progression through the induction of an epithelial-to-mesenchymal transition and metastasis. However, in a limited subset of tumors, SOX4 has also been reported to act as a tumor suppressor. These opposing roles suggest that the outcome of SOX4 activation depends on the cellular context and the tumor origin. Indeed, SOX4 expression, transcriptional activity and target gene specificity can be controlled by signaling pathways, including the transforming growth factor-β and the WNT pathway, as well as at the post-translational level through regulation of protein stability and interaction with specific cofactors, such as TCF, syntenin-1 and p53. Here, we provide an overview of our current knowledge concerning the role of SOX4 in tumor development and progression.
癌症的发生和发展是由转录网络的改变介导的，导致癌基因和肿瘤抑制基因活性的失衡。转录因子具有调节全局转录谱的能力，因此在肿瘤发生过程中，它们的表达和功能经常被发现失调。性别决定区 Y 相关高迁移率族盒转录因子 4（SOX4）是 SOX 转录因子 C 亚家族的成员，在胚胎发生过程中具有重要作用，其表达广泛，控制着许多组织的发育。SOX4 在多种肿瘤中表达升高，包括白血病、结直肠癌、肺癌和乳腺癌，表明其在这些恶性肿瘤的发生发展中具有重要作用。在许多癌症中，这种发育因子的失调表达与癌细胞增殖、细胞存活、抑制凋亡和肿瘤进展增加有关，通过诱导上皮-间充质转化和转移。然而，在有限的肿瘤亚群中，SOX4 也被报道作为肿瘤抑制因子。这些相反的作用表明，SOX4 激活的结果取决于细胞环境和肿瘤起源。事实上，SOX4 的表达、转录活性和靶基因特异性可以通过信号通路来控制，包括转化生长因子-β和 WNT 通路，以及通过调节蛋白质稳定性和与特定共因子（如 TCF、syntenin-1 和 p53）的相互作用来实现。在这里，我们概述了我们目前对 SOX4 在肿瘤发生和发展中的作用的认识。
