Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49306
Title: THE PLEIOTROPIC EFFECTS OF PTEN/AKT SIGNALING ON MITOCHONDRIAL RESPIRATORY FUNCTIONS
Authors: GOO CHONG KIAT
Keywords: 120485
Issue Date: 22-Aug-2013
Source: GOO CHONG KIAT (2013-08-22). THE PLEIOTROPIC EFFECTS OF PTEN/AKT SIGNALING ON MITOCHONDRIAL RESPIRATORY FUNCTIONS. ScholarBank@NUS Repository.
Abstract: While aerobic glycolysis has been shown to confer advantages in tumorigenesis, the molecular mechanisms underlying the regulation of this altered cancer metabolism remained elusive. Given that PTEN/Akt is one the of most dysregulated pathways in cancers, we sought to determine if there is any cross talk between this signaling and metabolism, particularly the mitochondrial respiratory functions. Using genetic modified mouse embryonic fibroblast (MEF), we showed that MEF with PTEN-/- had increased respiratory capacity, which was regulated specifically at translational but not transcriptional level. Dysregulated PTEN/Akt signaling in MEF and breast cell lines MCF10CA1a (malignant counterpart of MCF10A1) also had enhanced mitochondrial oxidative phosphorylation (OXPHOS) coupling (i.e. lower proton leak) mediated via mitochondrial cholesterol. The lower proton leak was associated with higher mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. The increased ROS production in PTEN/Akt dysregulated cells had elicited a higher dependency of those cells on glutamine metabolism. Given that glutamine metabolism is implicated in redox modulation, we further proposed that targeting redox regulation through glutamine metabolism has the potential in unveiling the Achilles' heel in cancers. Taken together, this study revealed the regulation of respiratory functions by PTEN/Akt signaling and its implication in tumorigenesis.
URI: http://scholarbank.nus.edu.sg/handle/10635/49306
Appears in Collections:Ph.D Theses (Open)

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