TY - JOUR
T1 - Mutant AKT1-E17K is oncogenic in lung epithelial cells
AU - De Marco, Carmela
AU - Malanga, Donatella
AU - Rinaldo, Nicola
AU - De Vita, Fernanda
AU - Scrima, Marianna
AU - Lovisa, Sara
AU - Fabris, Linda
AU - Carriero, Maria Vincenza
AU - Franco, Renato
AU - Rizzuto, Antonia
AU - Baldassarre, Gustavo
AU - Viglietto, Giuseppe
PY - 2015
Y1 - 2015
N2 - The hotspot E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. In this manuscript, we sought to determine whether this AKT1 variant is a bona-fide activating mutation and plays a role in the development of lung cancer. Here we report that in immortalized human bronchial epithelial cells (BEAS-2B cells) mutant AKT1-E17K promotes anchorage-dependent and -independent proliferation, increases the ability to migrate, invade as well as to survive and duplicate in stressful conditions, leading to the emergency of cells endowed with the capability to form aggressive tumours at high efficiency. We provide also evidence that the molecular mechanism whereby AKT1- E17K is oncogenic in lung epithelial cells involves phosphorylation and consequent cytoplasmic delocalization of the cyclin-dependent kinase (cdk) inhibitor p27. In agreement with these results, cytoplasmic p27 is preferentially observed in primary NSCLCs with activated AKT and predicts poor survival.
AB - The hotspot E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. In this manuscript, we sought to determine whether this AKT1 variant is a bona-fide activating mutation and plays a role in the development of lung cancer. Here we report that in immortalized human bronchial epithelial cells (BEAS-2B cells) mutant AKT1-E17K promotes anchorage-dependent and -independent proliferation, increases the ability to migrate, invade as well as to survive and duplicate in stressful conditions, leading to the emergency of cells endowed with the capability to form aggressive tumours at high efficiency. We provide also evidence that the molecular mechanism whereby AKT1- E17K is oncogenic in lung epithelial cells involves phosphorylation and consequent cytoplasmic delocalization of the cyclin-dependent kinase (cdk) inhibitor p27. In agreement with these results, cytoplasmic p27 is preferentially observed in primary NSCLCs with activated AKT and predicts poor survival.
KW - AKT1-E17K
KW - Human lung epithelial cells
KW - Lung cancer
KW - P27
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U2 - 10.18632/oncotarget.4022
DO - 10.18632/oncotarget.4022
M3 - Article
AN - SCOPUS:84950161642
VL - 6
SP - 39634
EP - 39650
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 37
ER -