Elucidating the Metabolic Plasticity of Cancer: Mitochondrial Reprogramming and Hybrid Metabolic States

Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Ins...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2018-03, Vol.7 (3), p.21
Main Authors: Jia, Dongya, Park, Jun Hyoung, Jung, Kwang Hwa, Levine, Herbert, Kaipparettu, Benny Abraham
Format: Article
Language:English
Subjects:
Cancer
cancer metabolism
Cell division
EMT
External stimuli
Fibroblasts
Genotype & phenotype
Glycolysis
hybrid metabolic phenotype
Macromolecules
metabolic plasticity
Metabolism
Metastases
metastasis
Mitochondria
mitochondrial respiration
Nuclei
Oxidative phosphorylation
OXPHOS
Phosphorylation
Plasticity
Post-translation
Retrograde transport
Review
stemness
tumorigenesis
Tumors
Warburg effect
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Summary:Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Instead, in highly aggressive cancer cells, mitochondrial energy pathways are reprogrammed to meet the challenges of high energy demand, better utilization of available fuels and macromolecular synthesis for rapid cell division and migration. Mitochondrial energy reprogramming is also involved in the regulation of oncogenic pathways via mitochondria-to-nucleus retrograde signaling and post-translational modification of oncoproteins. In addition, neoplastic mitochondria can engage in crosstalk with the tumor microenvironment. For example, signals from cancer-associated fibroblasts can drive tumor mitochondria to utilize OXPHOS, a process known as the reverse Warburg effect. Emerging evidence shows that cancer cells can acquire a hybrid glycolysis/OXPHOS phenotype in which both glycolysis and OXPHOS can be utilized for energy production and biomass synthesis. The hybrid glycolysis/OXPHOS phenotype facilitates metabolic plasticity of cancer cells and may be specifically associated with metastasis and therapy-resistance. Moreover, cancer cells can switch their metabolism phenotypes in response to external stimuli for better survival. Taking into account the metabolic heterogeneity and plasticity of cancer cells, therapies targeting cancer metabolic dependency in principle can be made more effective.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells7030021