Schwann cells in regeneration and cancer: an epithelial-mesenchymal transition perspective

In the peripheral nervous system, glial cells, known as Schwann cells (SCs), are responsible for supporting and maintaining nerves. One of the most important characteristics of SCs is their remarkable plasticity. In various injury contexts, SCs undergo a reprogramming process that generates specialized cells to promote tissue regeneration and repair. However, in pathological conditions, this same plasticity and regenerative potential can be hijacked. Different studies highlight the activation of the epithelial-mesenchymal transition (EMT) as a driver of SC phenotypic plasticity. Although SCs are not epithelial, their neural crest origin makes EMT activation crucial for their ability to adopt repair phenotypes, mirroring the plasticity observed during development. These adaptive processes are essential for regeneration. However, EMT activation in SCs-derived tumours enhances cancer progression and aggressiveness. Furthermore, in the tumour microenvironment (TME), SCs also acquire activated phenotypes that contribute to tumour migration and invasion by activating EMT in cancer cells. In this review, we will discuss how EMT impacts SC plasticity and function from development and tissue regeneration to pathological conditions, such as cancer.