LAUSR

Epithelial–mesenchymal transition (EMT) process epitomizes a change of cell phenotype that is typically reversible. Epithelial cells loosen cell–cell adhesion structures; including tight junctions, desmosomes, and adherens junctions, dismantle their polarity, and reorganize their cytoskeleton, switching from cytokeratins to vimentin intermediate filaments. Cells loosen connection to other cells and become individualized, motile, and resistant to apoptosis. The EMT process in vivo was initially defined as cellular remodeling occurring during in the embryo (Hay, 1968, 1995). EMT was observed in the formation of the heart valves (Markwald et al., 1975, 1977). The concept was extended to analogous progression occurring during the formation of mesoderm, neural crest, and loss of the Mullerian duct (Newgreen and Gibbins, 1982; Thiery et al., 1982; Trelstad et al., 1982). Early experimental work explored the tissue interactions mediating EMT in heart morphogenesis and the induction of mesenchyme from embryonic epithelia within collagen gels (Greenburg and Hay, 1982; Runyan and Markwald, 1983). From the original conceptualization, the EMT process has been implicated in multiple distinct physiological or pathological processes such as wound healing, carcinoma progression, and fibrosis, although displaying tissue-specific features. More specifically, EMT pathways were found to be involved in unsuspected processes, such as genomic integrity, chemotherapy resistance, metabolic balance, and cancer stem cell maintenance (Radisky et al., 2005; Mani et al., 2008; Haslehurst et al., 2012; Morandi et al., 2017). In this special issue, several newer aspects of EMT by cardiac endothelia are explored and/or reviewed. Current directions in the understanding of heart morphogenesis, valve formation, and cardiovascular diseases, linked to common signaling pathways that can go awry in several chapters (S anchez-Duffhues et al., 2017; Menon et al., 2018). The transcription factor, Runx2 has been of interest in cancer metastasis and is explored here in the context of EMT in the heart (Tavares et al., 2017). Fibrosis in the heart is linked to EMT of the endothelium, and this pathology is included here (Pesevski et al., 2017). Wound healing has long been considered an EMT-like process but has not been widely explored. A chapter here (Haensel and Dai, 2017) provides a review of cutaneous wound healing. Involvement of EMT-like processes during carcinoma progression is a live topic of discussion. It is discussed in several chapters, focusing on global investigation of EMT markers across 32 cancer types (Gibbons and Creighton, 2017) and TGF-b pathway roles (Ungefroren et al., 2017). Two chapters focus on EMT-like processes in lung cancer (Jolly et al., 2017; Otsuki et al., 2017). Newer links to ncRNA (Drak Alsibai and Meseure, 2017), circulating tumor cells (Francart et al., 2017), metabolism and myocardin related transcription factors (Garparics and Sebe, 2017) are discussed in following chapters. Finally, the decisive influence of tumor microenvironment, including mesenchymal cells (Schwab et al., 2017) and extracellular matrix (Tzanakakis et al., 2018) is commented. The alternation of EMT/MET cycles is emphasized, in regard to metastasis (Schwab et al., 2017). Finally an EMT model is introduced to explore in vivo aspects of the process, based on murine lens (Shirai et al., 2017). Together, these chapters provide a cross-section of investigations into EMT. They suggest that, whether described as EMT or EndoMT and with exploration in various developmental, fibrotic, or metastatic systems, there is both a core of common mechanisms and an opportunity to identify features that may be unique to subsets of cells undergoing this change in phenotype.