Nieszporek Artur, Skrzypek Klaudia, Adamek Grazyna, Majka Marcin
Jagiellonian University Medical College, Faculty of Medicine, Institute of Pediatrics, Department of Transplantation, Kraków, Poland.
Acta Biochim Pol. 2019 Dec 28;66(4):509-520. doi: 10.18388/abp.2019_2899.
Epithelial to mesenchymal transition (EMT) is a process during which cancer cells lose epithelial features, cytoskeletal architecture is re-organized, cell shape changes and cells activate genes that help to define mesenchymal phenotype, what leads to an increased cell motility and dissemination of tumor to distant metastatic sites. This review describes different signaling networks between microRNAs and proteins that regulate EMT in tumor growth. Activation of EMT is mediated via series of paracrine signaling molecules. WNT, TGF-b, NOTCH and Shh signaling pathways play crucial roles in activation of EMT-related transcription factors, such as SNAIL, SLUG, ZEB1/2 or TWIST. Recent data provide evidence that crosstalk between microRNAs, long non-coding RNAs and EMT-transcription factors is crucial event in EMT regulation. MicroRNAs affect also level of proteins responsible for cellular contact, adhesion and cytoskeletal proteins, what induces changes of epithelial to mesenchymal phenotype. Understanding of those signaling networks may help to identify novel biomarkers or develop new treatment strategies based on microRNA therapeutics in future.
上皮-间质转化(EMT)是一个过程,在此过程中癌细胞失去上皮特征,细胞骨架结构重新组织,细胞形状改变,并且细胞激活有助于定义间质表型的基因,这导致细胞运动性增加以及肿瘤扩散至远处转移部位。本综述描述了微小RNA与调节肿瘤生长中EMT的蛋白质之间的不同信号网络。EMT的激活是通过一系列旁分泌信号分子介导的。WNT、转化生长因子-β(TGF-β)、NOTCH和音猬因子(Shh)信号通路在激活EMT相关转录因子(如SNAIL、SLUG、锌指E盒结合蛋白1/2(ZEB1/2)或TWIST)中起关键作用。最近的数据表明,微小RNA、长链非编码RNA与EMT转录因子之间的相互作用是EMT调节中的关键事件。微小RNA还影响负责细胞接触、黏附的蛋白质以及细胞骨架蛋白的水平,这诱导了上皮到间质表型的变化。了解这些信号网络可能有助于识别新的生物标志物或在未来基于微小RNA疗法开发新的治疗策略。