ETS 转录因子介导的肿瘤发生的分子机制。
Molecular mechanisms of ETS transcription factor-mediated tumorigenesis.
机构信息
Cancer Biology Training Program .
出版信息
Crit Rev Biochem Mol Biol. 2013 Nov-Dec;48(6):522-43. doi: 10.3109/10409238.2013.838202. Epub 2013 Sep 25.
Abstract
The E26 transformation-specific (ETS) family of transcription factors is critical for development, differentiation, proliferation and also has a role in apoptosis and tissue remodeling. Changes in expression of ETS proteins therefore have a significant impact on normal physiology of the cell. Transcriptional consequences of ETS protein deregulation by overexpression, gene fusion, and modulation by RAS/MAPK signaling are linked to alterations in normal cell functions, and lead to unlimited increased proliferation, sustained angiogenesis, invasion and metastasis. Existing data show that ETS proteins control pathways in epithelial cells as well as stromal compartments, and the crosstalk between the two is essential for normal development and cancer. In this review, we have focused on ETS factors with a known contribution in cancer development. Instead of focusing on a prototype, we address cancer associated ETS proteins and have highlighted the diverse mechanisms by which they affect carcinogenesis. Finally, we discuss strategies for ETS factor targeting as a potential means for cancer therapeutics.
摘要
E26 转化特异性 (ETS) 转录因子家族对于发育、分化、增殖至关重要，在细胞凋亡和组织重塑中也发挥作用。因此， ETS 蛋白表达的变化对细胞的正常生理机能有重大影响。ETS 蛋白通过过度表达、基因融合和 RAS/MAPK 信号转导的调节而发生的转录后变化与正常细胞功能的改变有关，并导致无限增殖、持续的血管生成、侵袭和转移。现有数据表明，ETS 蛋白控制上皮细胞和基质区室中的途径，两者之间的串扰对于正常发育和癌症是必需的。在这篇综述中，我们集中讨论了已知在癌症发展中起作用的 ETS 因子。我们没有关注一个原型，而是针对与癌症相关的 ETS 蛋白，并强调了它们影响致癌作用的多种机制。最后，我们讨论了 ETS 因子靶向作为癌症治疗的潜在手段的策略。
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