11 - The Continuum of Epithelial Mesenchymal Transition – Implication of Hybrid States for Migration and Survival in Development and Cancer

Summary

EMT AND CELL MIGRATION – EMBRYONIC NECESSITIES CO-OPTED BY INVASIVE CANCER

The concept of the epithelial–mesenchymal transition (EMT) originated from studies of events in development, particularly those preceding the onset of cell migration [1]. These were initially brought together and popularized by the efforts of the late Elizabeth Hay and colleagues [2, 3]. One of the most intensively studied examples of EMT and cell migration is the generation of migratory neural crest mesenchyme from the neurectodermal epithelium [4] (Figure 11.1). These cells go on to form the autonomic and sensory nervous systems. Even prior to this, the emergence of the primary mesenchyme from the epithelial epiblast during gastrulation (the first EMT) results in the formation of highly motile cells that are critical to the development of the body plan [1] (Figure 11.2A). Further EMTs occur in other epithelia after the neural crest EMT to generate the cells that form muscle, bone, and connective tissues (Figure 11.2B). Such cellular plasticity is fundamental to embryological development and is regulated largely at the transcriptional level. Various transcriptional repressors of E-cadherin (and other cadherins), such as Snail (Snail 1), Slug (Snail 2), Twist, Zeb1 (δEF1), Zeb2 (SIP), and E47/E12, regulate EMT in developmental system (reviewed in [5]).

Commitment to lineage differentiation in normal cells is more pliant than first thought, and cellular transition is emerging as a major mechanism of adult tissue homeostasis [6].