恶性间叶肿瘤的间叶-上皮表型转化研究进展

Mesenchymal to epithelial transition in malignant mesenchymal tumors

相对于上皮性肿瘤的上皮-间叶表型转化(epithelial to mesenchymal transition,EMT)及间叶-上皮表型转化(mesen-chymal to epithelial transition,MET)的研究,恶性间叶性肿瘤中MET相关研究较少。MET在分子水平上反映为上皮性标志物如E-钙粘素E-cadherin的上调和间叶性标志物如波形蛋白Vimentin的下调,其过程涉及始动信号、转录因子调节、表面标志物的改变、信号通路改变等多个环节。本文概述了恶性间叶肿瘤中与MET紧密相关的TGF-β等始动因素、SNAI等关键转录因子、mi RNA调节因素对重要细胞信号通路等影响及MET对肿瘤的演进及转归的影响等方面的研究,为针对MET的临床应用奠定基础。

Mesenchymal to epithelial transition （MET）, whereby mesenchymal cells become more epithelial like in phenotype, was observed to occur during normal development and in cancers. Numerous investigations have been conducted on MET in carcino-mas. In addition, accumulating evidence also suggests the critical function of MET in sarcomas. Integrated analyses reveal that MET may be an important biological and clinical process in sarcomas, and transcription factors such as Slug may also perform central func-tions in epithelial differentiation in several sarcomas such as leiomyo-sarcoma and synovial sarcoma. Given the scarcity of investiga-tions and evidence, several important issues about MET, such as its molecular markers, signaling mechanisms, micro RNA regulations, and clinical significance, need to be clarified. In this article, we review several important questions about MET in sarcomas, including molecular markers, signaling mechanisms, regulation by miRNAs, and therapeutic implications.