The epithelial–mesenchymal transition (EMT) program is critical to metastatic cancer progression. EMT results in the expression of mesenchymal proteins and enhances migratory and invasive capabilities. In a small percentage of cells, EMT results in the expression of stemness-associated genes that provide a metastatic advantage. Although EMT had been viewed as a binary event, it has recently become clear that the program leads to a spectrum of phenotypes, including hybrid epithelial/mesenchymal (E/M) cells that have significantly greater metastatic capability than cells on the epithelial or mesenchymal ends of the spectrum. As hybrid E/M cells are rarely observed in physiological, non-diseased states in the adult human body, these cells are potential biomarkers and drug targets. Hybrid E/M cells are distinguished by the co-expression of epithelial and mesenchymal proteins, such as the intermediate filament proteins cytokeratin (CK; epithelial) and vimentin (VIM; mesenchymal). Although these intermediate filaments have been extensively used for pathological characterization and detection of aggressive carcinomas, little is known regarding the interactions between CK and VIM when co-expressed in hybrid E/M cells. This review describes the characteristics of hybrid E/M cells with a focus on the unique co-expression of VIM and CK. We will discuss the structures and functions of these two intermediate filament proteins and how they may interact when co-expressed in hybrid E/M cells. Additionally, we review what is known about cell-surface expression of these intermediate filament proteins and discuss their potential as predictive biomarkers and therapeutic targets.
上皮-间质转化(EMT)程序对转移性癌症进展至关重要。EMT导致间质蛋白表达并增强迁移和侵袭能力。在少数细胞中,EMT会引发干细胞相关基因的表达,从而提供转移优势。尽管EMT曾被视为二元事件,但最近研究表明该程序会导致一系列表型,包括上皮/间质混合(E/M)细胞,这些细胞比上皮或间质谱系两端的细胞具有显著更强的转移能力。由于混合E/M细胞在成年人体生理非疾病状态下极少出现,这些细胞具有作为生物标志物和药物靶点的潜力。混合E/M细胞的特征在于上皮和间质蛋白的共表达,例如中间丝蛋白细胞角蛋白(CK;上皮性)和波形蛋白(VIM;间质性)。尽管这些中间丝蛋白已广泛用于侵袭性癌的病理特征描述和检测,但对于CK和VIM在混合E/M细胞中共表达时的相互作用知之甚少。本综述描述了混合E/M细胞的特征,重点关注VIM和CK的独特共表达现象。我们将讨论这两种中间丝蛋白的结构与功能,以及它们在混合E/M细胞中共表达时可能发生的相互作用。此外,我们回顾了关于这些中间丝蛋白细胞表面表达的现有认知,并探讨其作为预测性生物标志物和治疗靶点的潜力。