33P - Isoform-Specific Functions in Pancreatic Adenocarcinoma

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Basic Science
Pancreatic Cancer
Presenter Hugo Arasanz
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors H. Arasanz1, M. Zuazo-Ibarra2, M. Gato-Cañas2, M. Ibáñez-Vea2, G. Fernández-Hinojal1, J. Fernández-Irigoyen3, E. Santamaria3, G. Kochan2, R. Vera1, D. Escors2
  • 1Medical Oncology, Complejo Hospitalario de Navarra, 31008 - Pamplona/ES
  • 2Immunomodulation, Navarrabiomed, Pamplona/ES
  • 3Proteomics, Navarrabiomed, Pamplona/ES



AKT/PKB is a protein kinase that plays a key role in cancer, which is expressed as 3 isoforms: AKT1 (PKBα), AKT2 (PKBβ) and AKT3 (PKBγ). Although these isoforms are remarkably similar, there is evidence that each isoform yields specific functions which may vary depending on the cell type. Even so, the underlying molecular pathways specifically regulated by each one of them are unknown.


To gain insight into the role of each isoform in the biology of human pancreatic adenocarcinoma cells, we have silenced each AKT isoform individually using short hairpin RNAs (shRNAs) delivered by lentiviral transduction. Cells transduced with an unspecific shRNA were used as controls. Then, high-throughput quantitative proteomic analyses were performed to evaluate the differential signaling routes altered by silencing of each AKT isoform.


AKT1 silencing induced the upregulation of 57 proteins and downregulation of 58. AKT2 silencing up-regulated and down-regulated 78 and 101 respectively. AKT3 silencing resulted in the upregulation of 88 and downregulation of 93. The expression levels of 45 proteins were altered exclusively after AKT1 knockdown, while 74 proteins and 89 were specifically altered for AKT2 and AKT3 silencing, respectively. AKT1 silencing up-regulated RNA splicing, GPCR and mTOR pathways, and mitochondrial functions such as the respiratory chain, fatty acid metabolism or mitochondrial DNA synthesis. Pathways related to apoptosis and cell migration were inhibited. AKT2 silencing caused the activation of pathways related to apoptosis, splicing, protein folding and some mitochondrial functions. In contrast, other key metabolic pathways such as nucleic acid synthesis, pentose phosphate pathway, cell adhesion and PI3K signalling were down-modulated. Lastly, AKT3 silencing induced increased splicing and mitochondrial functions, regulation of gene expression and snRNA processing. In this case, the pentose phosphate pathway, cell adhesion, apoptosis, protein synthesis and nucleic acid synthesis were also inhibited.


AKT isoforms have specific functions in pancreatic adenocarcinoma. The individual silencing of each isoform induces a differential alteration of molecular pathways involved in main cellular processes.

Clinical trial identification

Legal entity responsible for the study

D. Escors




All authors have declared no conflicts of interest.