Department of Surgery I, Charité School of Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany.
Anticancer Agents Med Chem. 2011 Jun;11(5):448-54. doi: 10.2174/187152011795677436.
Epithelial to mesenchymal transition (EMT) is a biological process that allows well-differentiated, polarized epithelial cells to undergo a conversion to motile, unpolarized mesenchymal cells. EMT plays crucial roles during implantation, embryogenesis, and organ development (Type 1 EMT), is associated with tissue regeneration and organ fibrosis (Type 2 EMT), and involved in cancer invasion, metastasis, and drug resistance (Type 3 EMT). Since aggressiveness and drug resistance are hallmarks of ductal pancreatic cancer, significant effort has been undertaken in recent years to elucidate molecular EMT mechanisms in this dismal malignancy. This represents a formidable challenge for several reasons: EMT is a dynamic process, both with regard to spatial and temporal heterogeneity. Moreover, EMT is induced and regulated by a complex network of traditional signaling pathways and new players like microRNAs. Interestingly, similar molecular characteristics link EMT-type cells also to the concept of cancer stem cells. This review tries to integrate the current knowledge regarding EMT and pancreatic cancer; furthermore to outline not only the perspective on novel EMT-associated therapeutic targets, but also on overcoming drug resistance by interfering with EMT.
上皮间质转化（EMT）是一种生物学过程，它使分化良好、极化的上皮细胞经历向运动、非极化的间充质细胞的转化。EMT 在植入、胚胎发生和器官发育（1 型 EMT）中发挥关键作用，与组织再生和器官纤维化（2 型 EMT）有关，并参与癌症侵袭、转移和耐药性（3 型 EMT）。由于侵袭性和耐药性是导管胰腺癌的特征，近年来，人们为阐明这种恶性肿瘤中 EMT 的分子机制做出了巨大努力。这是一个巨大的挑战，原因有几个：EMT 是一个动态过程，无论是在空间还是时间上都具有异质性。此外，EMT 是由传统信号通路和新的参与者（如 microRNAs）组成的复杂网络诱导和调节的。有趣的是，类似的分子特征将 EMT 样细胞与癌症干细胞的概念联系起来。这篇综述试图整合目前关于 EMT 和胰腺癌的知识；此外，不仅概述了新型 EMT 相关治疗靶点的前景，还概述了通过干扰 EMT 来克服耐药性的前景。
