title: Mutant AKT1-E17K is oncogenic in lung epithelial cells.
abstract: 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.
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Graecia", Catanzaro, Italy.|BIOGEM-Institute of Genetic Research, Ariano Irpino, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: De Marco
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Graecia", Catanzaro, Italy.|BIOGEM-Institute of Genetic Research, Ariano Irpino, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Malanga
authors.affiliation: BIOGEM-Institute of Genetic Research, Ariano Irpino, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Rinaldo
authors.affiliation: BIOGEM-Institute of Genetic Research, Ariano Irpino, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: De Vita
authors.affiliation: BIOGEM-Institute of Genetic Research, Ariano Irpino, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Scrima
authors.affiliation: Experimental Oncology 2, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lovisa
authors.affiliation: Experimental Oncology 2, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Fabris
authors.affiliation: Experimental Oncology, IRCCS Fondazione Pascale, Napoli, Italy.
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Carriero
authors.affiliation: Experimental Oncology, IRCCS Fondazione Pascale, Napoli, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" Medical School, Catanzaro, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Rizzuto
authors.affiliation: Experimental Oncology 2, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baldassarre
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Graecia", Catanzaro, Italy.|BIOGEM-Institute of Genetic Research, Ariano Irpino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viglietto
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020125:Mutation, Missense; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D059008:Time-Lapse Imaging; D014183:Transplantation, Heterologous
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT1-E17K; human lung epithelial cells; lung cancer; p27