Antagonism between FOXO and MYC Regulates Cellular Powerhouse

Alterations in cellular metabolism are a key feature of the transformed phenotype. Enhanced macromolecule synthesis is a prerequisite for rapid proliferation but may also contribute to induction of angiogenesis, metastasis formation, and tumor progression, thereby leading to a poorer clinical outcom...

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Published in:Frontiers in oncology Vol. 3; p. 96
Main Authors: Peck, Barrie, Ferber, Emma C., Schulze, Almut
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 01.01.2013
Subjects:
Cancer
HIF
hypoxia
Metabolism
Mitochondria
Oncology
ROS
FOXO
hypoxia
HIF
MYC
mitochondria
ROS
cancer
metabolism
ISSN:2234-943X, 2234-943X
Online Access:Get full text
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Summary:Alterations in cellular metabolism are a key feature of the transformed phenotype. Enhanced macromolecule synthesis is a prerequisite for rapid proliferation but may also contribute to induction of angiogenesis, metastasis formation, and tumor progression, thereby leading to a poorer clinical outcome. Metabolic adaptations enable cancer cells to survive in suboptimal growth conditions, such as the limited supply of nutrient and oxygen often found in the tumor microenvironment. Metabolic changes, including activation of glycolysis and inhibition of mitochondrial ATP production, are induced under hypoxia to promote survival in low oxygen. FOXO3a, a transcription factor that is inhibited by the phosphatidylinositol 3-kinase/Akt pathway and is upregulated in hypoxia, has emerged as an important negative regulator of MYC function. Recent studies have revealed that FOXO3a acts as a negative regulator of mitochondrial function through inhibition of MYC. Ablation of FOXO3a prevents the inhibition of mitochondrial function induced by hypoxia and results in enhanced oxidative stress. This review will focus on the antagonism between FOXO3a and MYC and discuss their role in cellular bioenergetics, reactive oxygen metabolism, and adaptation to hypoxia, raising questions about the role of FOXO proteins in cancer.
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Edited by: Eric W. Lam, Imperial College London, UK
This article was submitted to Frontiers in Molecular and Cellular Oncology, a specialty of Frontiers in Oncology.
Reviewed by: Emilio Hirsch, University of Torino, Italy; Sonia Lain, Karolinska Institutet, Sweden; Sebastien Dupasquier, Université Catholique de Louvain, Belgium
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2013.00096