“…The PI3K-AKT pathway in cancer has been shown to inhibit apoptosis (Zilberman et al, 2009 ). In previous studies, it has been proposed that AKT1(E17K) mutations induce proprioceptive activation by localizing to the stromal membrane in a PI3K-independent manner (Brugge et al, 2007 ; Do et al, 2008 ), promote regeneration and activation of the cell membrane (Furukawa et al, 2005 ; Shi and Hruban, 2012 ; Garcia-Carracedo et al, 2013 ), and stimulate PI3K-AKT signaling, resulting in uncontrolled cell proliferation, increased cell survival, and accelerated cellular invasion (Keniry and Parsons, 2008 ; Guo et al, 2010 ; Lauring et al, 2010 ; Mancini et al, 2016 ; De Marco et al, 2017 ). It was shown that the E17K mutation not only promotes membrane localization, but that in the absence of serum the mutant cells exhibit enhanced phosphorylation of serine 473 (Ser473) and threonine 308 (Thr308) [a conformational change after AKT-forming plasma membrane targeting that exposes two key amino acids (Vivanco and Sawyers, 2002 ; Landgraf et al, 2008 )], resulting in constitutive activation of Akt1 (Askham et al, 2010 ).…”