Spatial and Temporal Relationship between Epithelial-Mesenchymal Transition (EMT) and Stem Cells in Cancer.

Abstract

Epithelial-mesenchymal transition (EMT) is often linked with carcinogenesis. However, EMT is also important for embryo development and only reactivates in cancer. Connecting how EMT occurs during embryonic development and in cancer could help us further understand the root mechanisms of cancer diseases. There are key regulatory elements that contribute to EMT and the induction and maintenance of stem cell properties during embryogenesis, tissue regeneration, and carcinogenesis. Here, we explore the implications of EMT in the different stages of embryogenesis and tissue development. We especially highlight the necessity of EMT in the mesodermal formation and in neural crest cells. Through EMT, these cells gain epithelial-mesenchymal plasticity (EMP). With this transition, crucial morphological changes occur to progress through the metastatic cascade as well as tissue regeneration after an injury. Stem-like cells, including cancer stem cells, are generated from EMT and during this process upregulate factors necessary for stem cell maintenance. Hence, it is important to understand the key regulators allowing stem cell awakening in cancer, which increases plasticity and promotes treatment resistance, to develop strategies targeting this cell population and improve patient outcomes. EMT involves multifaceted regulation to allow the fluidity needed to facilitate adaptation. This regulatory mechanism, plasticity, involves many cooperating transcription factors. Additionally, posttranslational modifications, such as splicing, activate the correct isoforms for either epithelial or mesenchymal specificity. Moreover, epigenetic regulation also occurs, such as acetylation and methylation. Downstream signaling ultimately results in the EMT which promotes tissue generation/regeneration and cancer progression.