Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process

Epithelial-mesenchymal transition (EMT) is a critical process in the development of many tissues and organs in multicellular organisms that its important role in the pathogenesis of metastasis and tumor cell migration has been firmly established. Decreased adhesive capacity, cytoskeletal reorganization, and increased mobility are hallmarks of the EMT. Several molecular mechanisms promote EMT, Including regulation of the levels of specific cell-surface proteins, ECM-degrading enzymes, and altering the expression of certain transcription factors and microRNAs. EMT process is modulated through multiple signaling pathways including the AKT/mTOR pathway. AKT is a key component in numerous processes which was recently shown to regulate the EMT through suppression of the expression of E-cadherin via EMT transcription factors. On the other hand, mTOR complexes can also regulate the EMT through the regulation of cell's actin cytoskeleton by altering the PKC phosphorylation state and direct phosphorylation and activation of Akt. Here we review the effect of AKT and mTOR on EMT and consequently metastasis and cell motility. (C) 2019 Published by Elsevier B.V.