Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Abstract

The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.

Keywords: Cell migration; EMT; P1 receptors; P2 receptors; Purinergic signaling.

Fig. 1

Main characteristics of epithelial and mesenchymal phenotypes and their modulation by purinergic receptors. PI3K, Phosphatidylinositol 3-kinase; AKT, protein kinase B; VEGF, vascular endothelial growth factor; EGFR, epithelial growth factor receptor; ERK, p42/p44 mitogen-activated protein kinases; PKC, protein kinase C; TGF-β, transforming growth factor beta; IL-6, interleukin 6; α-SMA, alpha smooth muscle actin; cAMP, cyclic adenosine monophosphate; Fli-1, ETS transcription factor; CTGF, connective tissue growth factor. Based in the references – for P2X7, 78–83 for P2Y2, 93–95 for P2Y6, 92 for P2Y12, 128 for ADORA2B, 129–131 and 135 for ADORA 2A and 132 for ADORA3