The Epithelial-Mesenchymal Transition is an embryonic key developmental program that is often activated during cancer invasion and metastasis. It is a process by which cells undergo a morphological switch from the epithelial polarized phenotype to the mesenchymal fibroblastoid phenotype. As a result of EMT, epithelial cells lose their defined cell�Ccell/cell�C substratum contacts and their structural/functional polarity, and they become spindle shaped and morphologically similar to activated fibroblasts. At the molecular level, EMT is defined by the loss of cell�Ccell adhesion molecules, down-regulation of epithelial differentiation markers including cytokeratins and E-cadherin and transcriptional induction of mesenchymal markers such as vimentin, fibronectin and Ncadherin with a nuclear localization of beta-catenin. Nuclear beta-catenin induces a gene expression pattern favouring tumour invasion, and mounting evidence indicates multiple reciprocal interactions of E-cadherin and beta-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumour cells. Other genes involved in EMT are Snail, Twist e SIP-1/ZEB-2, all repressors of gene CDH1 that codes for E-cadherin. Several distinct traits have been conveyed by EMT, including cell motility, invasiveness, resistance to apoptosis, and some properties of stem cells. Many signalling pathways have contributed to the induction of EMT, including transforming growth factor-beta, Wnt, Hedgehog, Notch, and nuclear factor-kappa B. Kyoung-Ok Hong et al. have shown that activation of PI3K/ Akt axis is one of the key mechanisms in the process of EMT and it seems that its inhibition by treatment with phosphatidylinositol ether lipid PF 04449613 analogues may regulate the reverse process Mesenchymal Epithelial reverse Transition leading to the re-expression of both E-cadherin and b-catenin, and reducing expression of vimentin, mesenchymal marker, in oral squamous lines carcinoma stabilized. During the process of tumour metastasis, which is often enabled by EMTs, disseminated cancer cells would seem to require self-renewal capability, similar to that exhibited by stem cells, in order to spread macroscopic metastases. This raises the possibility that the EMT process, which enables cancer cell dissemination, may also impart a self-renewal capability to disseminating cancer cells. Indeed, the metastatic process is at least superficially similar to the processes that occur during PI 828 tissue repair and regeneration and enable adult stem cells to exit tissue reservoirs such as the bone marrow, enter and survive in the circulation, and get into secondary tissue sites, where they proliferate, differentiate, and participate in tissue reconstruction.