Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Biochim Biophys Acta Rev Cancer. 2018 Dec;1870(2):151-157. doi: 10.1016/j.bbcan.2018.07.001. Epub 2018 Jul 8.
Metastasis is the leading cause of mortality among cancer patients. Dissemination enabled by an epithelial-to-mesenchymal transition (EMT) of carcinoma cells has long been considered to be the predominant mechanism for carcinoma metastasis, based on overexpression studies of many EMT-inducing transcription factors. Individual CTCs - and a binary framework of EMT - have been long considered to be sufficient and necessary condition for metastasis. However, recent studies have shown that collective migration and invasion through tumor buds and clusters of Circulating Tumor Cells (CTCs) as possibly being the prevalent mode of metastasis, although individual CTCs may still contribute to metastasis. These strands and clusters have been proposed to often exhibit a hybrid epithelial/mesenchymal (E/M) phenotype where cells retain epithelial traits of cell-cell adhesion and simultaneously gain mesenchymal characteristics of migration and invasion. To highlight the crucial questions regarding metastasis, we define EMT in a non-binary and context-specific manner, suggest that it can be viewed as a trans-differentiation process, and illustrate the implications of hybrid E/M phenotype(s) and cluster-based dissemination in metastasis.
转移是癌症患者死亡的主要原因。基于许多 EMT 诱导转录因子的过表达研究，癌 细胞的上皮-间充质转化（EMT）被认为是癌转移的主要机制，这使得癌细胞的扩散成为可能。单个循环肿瘤细胞（CTC）和 EMT 的二元框架长期以来被认为是转移的充分和必要条件。然而，最近的研究表明，通过肿瘤芽和循环肿瘤细胞（CTC）簇的集体迁移和侵袭可能是转移的主要模式，尽管单个 CTC 仍可能有助于转移。这些链和簇经常表现出混合上皮/间充质（E/M）表型，其中细胞保留上皮细胞的细胞间粘附特性，同时获得迁移和侵袭的间充质特征。为了强调转移的关键问题，我们以非二元和特定于上下文的方式定义 EMT，认为它可以被视为一种转分化过程，并说明混合 E/M 表型和基于簇的扩散在转移中的意义。
