, 2004). The Akt family of kinases, i.e., Akt1, Akt2, and Akt3, plays arolein processes that are well known as hallmarks of cancer, such as sustained angiogenesis, unlimited replicative potential, and tissue invasion and metastasis (Hanahan and Weinberg, 2011). Moreover, Akt activation mediates

the expression of N-cadherin and metalloproteinases and plays aroleintum or invasion and metastasis by inducing EMT (Park et al., 2001, Higuchi et al., 2001, Grille et al., 2003 and Wallerand et al., 2010). Recently, Steelman et al. (2011) demonstrated that the activation of AKT-1 increased the resistance of MCF-7 cells to radiation. Additionally, Toker and Yoeli-Lerner (2006) showed that Akt1 might have a dual role in tumorigenesis, not only promoting it by suppressing apoptosis but also inhibiting it by suppressing invasion and metastasis. The specific role of AKT in terms of cell motility and invasion seems check details to depend on the cell type and the pathways that are activated. Many of the enzymes that either mediate the

Akt signal, such as MDM2 (Zhou et al., 2001), or regulate Akt activity, such as the tumor suppressor PTEN (Li et al., 1997), are frequently mutated in human tumors. As such, Akt activity is up-regulated, thus increasing tumor cell growth and survival. In several mammalian systems, activated Akt1 correlates with cell migration and invasion. While constitutively active Akt1 can enhance the ability of some cells to invade (Steelman et al., 2011, Kim et al., 2001 and Arboleda et al., 2003), Akt1 can also have the Alectinib ic50 opposite effect

in normal or less invasive cells (Arboleda et al., 2003). Moreover, the increased activation of Akt1 correlates with increased proliferation and anchorage-independent growth. However, the effects of activated Akt1 on cell migration and invasiveness depend on the type of cells and tissues in which its action is being studied (Steelman et al., 2011, Kim et al., 2001, Arboleda et al., 2003, Enomoto et al., 2005, Irie et al., 2005 and Yoeli-Lerner et al., 2005). Yoeli-Lerner et al. (2005) and Toker and Yoeli-Lerner (2006) revealed that the expression of activated Gemcitabine Akt1 potently blocks the migration and invasion of three distinct breast cancer cell lines through Matrigel in vitro. In fibroblasts, Akt signaling enhances the activation of various small GTPases, leading to remodeling of the actin cytoskeleton and enhancing cell motility ( Enomoto et al., 2005). Similarly, the expression of activated Akt in fibrosarcoma or pancreatic cancer cells increases their ability to invade through Matrigel ( Park et al., 2001 and Kim et al., 2001). Liu et al. (2006) demonstrated that cells expressing activated Akt1 show increased proliferation and resistance to apoptosis. Additionally, the invasiveness and motility of the cells were substantially decreased by the down-regulation of Rho activity.