Epithelial-mesenchymal transition and metastasis: Role of dicer expression

Abstract

Epithelial-Mesenchymal Transition (EMT) is a major cellular process involved at the very fi rst steps of the development. Recent work strongly implicates EMT in cancer progression as well as initiation. The role of EMT during metastatic process has long been controversial since pathologists failed to detect mesenchymal cells in carcinomas. Now, data clearly show the presence of mesenchymal and dedifferentiated cells at the invasive front of some solid tumors. The extra and intracellular signals that lead to EMT are only starting to be understood. Ultimately, every EMTinducing pathway will activate any of the E-cadherin transcriptional repressors (Zeb1, Zeb2, Twist, Snail or Slug). Some of these repressors were found over-expressed in cancer and their expression correlates with the presence of metastases. Recently, studies have implicated the siRNA/miRNA biogenesis enzyme Dicer in EMT and metastatic progression. Dicer inhibition promotes metastasis while restoring its expression suppresses metastasis. Decreased Dicer expression leads to Zeb1/Zeb2 proteins increased expression and EMT induction. Due to its central role in neuronal regulation cell fate and the importance of miRNA biogenesis in neuronal differentiation, an important direction for future research may involve determining whether Dicer has metastasis-suppressive role in Central Nervous System cancers.