05), respectively. Discussion During EMT, epithelial cells acquire fibroblast-like properties and exhibit reduced cell-cell adhesion and increased motility. The plasticity afforded by the EMT is central to the complex remodeling of embryo and organ architecture during gastrulation and organogenesis. In pathological processes such as oncogenesis, the EMT may endow cancer cells with enhanced motility and invasiveness. Indeed, oncogenic transformation may be associated with signaling pathways promoting the EMT [22]. Akt activation is frequent in human epithelial cancer. In our previous study [23], Akt

activation in OSCC was linked to aggressive clinical behavior selleck chemicals and the loss of histological features of epithelial differentiation. These findings are consistent with Akt directly affecting epithelial cell morphology, cell motility, and invasiveness. Grille et al. [24] demonstrated that OSCC cells engineered to express constitutively active Akt underwent EMT, characterized by downregulation of the epithelial markers desmoplakin, E-cadherin, and beta-catenin, and upregulation of the mesenchymal marker vimentin. The cells also lost their epithelial cell morphology

and acquired fibroblast-like properties. In addition, the cells expressing constitutively active Akt exhibited reduced cell-cell adhesion, increased motility on fibronectin-coated Torin 2 nmr surfaces, and increased invasiveness in animals. Because OSCC cells engineered to express constitutively active Akt have been known to undergo EMT, we tried

to examine whether inhibition of Akt activity could restore epithelial characteristics and deplete mesenchymal features. In the present study, PIA treatment induced the expression and cytoplasmic localization of the epithelial markers (E-cadherin and β-catenin). In addition, it decreased the vimentin expression and localization, although the change was not as prominent as that in the epithelial markers. Also, the inhibition of Akt activity restored the polygonal epithelial morphology and reduced the migratory ability. This indicates that the inhibition of Akt activity could induce the MErT in Methane monooxygenase OSCC cells, and that the gain of epithelial characteristic might earlier or more prominent event in the MErT of the OSCC than the loss of mesenchymal one. Several EMT-inducing developmental regulators repress E-cadherin transcription via interaction with specific E-boxes of the proximal E-cadherin promoter [25, 26]. The Snail-related zinc-finger transcription factors (Snail and Slug), the (more distantly related) repressor SIP-1/ZEB-2, and the related Snail family member δ EF-1/ZEB1 are the most prominent [27–30]. The Snail protein is one of the key molecules in the EMT and its expression is inversely correlated with E-cadherin expression in a number of cancers, including OSCC [31–33]. Accordingly, inhibition of Akt activity induced downregulation of EMT-related transcription factor Snail.