Profound Reprogramming towards Stemness in Pancreatic Cancer Cells as Adaptation to AKT Inhibition.

ABSTRACT: Cancer cells acquire resistance to cytotoxic therapies targeting major survival pathways by adapting their metabolism. The AKT pathway is a major regulator of human pancreatic adenocarcinoma progression and a key pharmacological target. The mechanisms of adaptation to long-term silencing of AKT isoforms of human and mouse pancreatic adenocarcinoma cancer cells were studied. Following silencing, cancer cells remained quiescent for long periods of time, after which they recovered proliferative capacities. Adaptation caused profound proteomic changes largely affecting mitochondrial biogenesis, energy metabolism and acquisition of a number of distinct cancer stem cell (CSC) characteristics depending on the AKT isoform that was silenced. The adaptation to AKT1 silencing drove most de-differenti

SUBMITTER: Arasanz H 

PROVIDER: S-EPMC7464748 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature