![]() 8, 9 An intermediate state implies a spectrum of heterogeneity for EMT (rather than two extreme ends of the process), with potentially metastable, plastic intermediate cells. 1, 3 However, studies usually overlook the progressive changes during intermediate cellular states. 6, 7 Fluctuations in several molecular markers are commonly used to assess the EMT status, such as an increase in the mesenchymal marker, vimentin and/or a decrease in the epithelial markers, E-cadherin and cytokeratin. 2 EMT describes a process that controls the progressive loss of epithelial characteristics and the acquisition of mesenchymal features, 3 as well as the acquisition of chemoresistance, 4 immune escape 5 and the maintenance of cancer stemness. 1 The EMT programme contributes to the dissemination of carcinoma cells from solid tumours and the formation of micro-metastatic foci that subsequently develop into clinically detectable metastases. The concept of the EMT Spectrum allows the utilisation of EMT genes as predictive markers and the design and application of therapeutic targets for reversing EMT in a selective subgroup of patients.Įpithelial–mesenchymal transition (EMT), a fundamental mechanism in embryonic development, is crucial in carcinoma progression. We conclude that the characterisation of intermediate EMT states provides a new approach to better define EMT. We show how a 33-gene EMT Signature can sub-classify an OC cohort into four EMT States correlating with progression-free survival (PFS). A specific Src-kinase inhibitor, Saracatinib (AZD0530), restores E-cadherin expression in Intermediate M cells in in vitro and in vivo models and abrogates spheroidogenesis. In cell-based EMT-related functional studies, OC cells harbouring an Intermediate M phenotype are characterised by high N-cadherin and ZEB1 expression and low E-cadherin and ERBB3/HER3 expression and are more anoikis-resistant and spheroidogenic. ![]() Phenotypic EMT characterisation reveals four subgroups: Epithelial, Intermediate E, Intermediate M and Mesenchymal, which represent different epithelial–mesenchymal compositions along the EMT spectrum. In this study, we describe a model system for appraising the spectrum of EMT using 43 well-characterised OC cell lines. Numerous studies have focused on bona fide epithelial and mesenchymal states but rarely on intermediate states. Different degrees of epithelial–mesenchymal transition (EMT) have been found to occur in carcinomas from breast, colon and ovarian carcinoma (OC), among others. The phenotypic transformation of well-differentiated epithelial carcinoma into a mesenchymal-like state provides cancer cells with the ability to disseminate locally and to metastasise.
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