Mitochondrial Fission Induces Glycolytic Reprogramming in Cancer-Associated Myofibrobla... - 0 views
www.ncbi.nlm.nih.gov/...PMC3478457
warburg effect Cancer cancer associated fibroblasts CAFs reverse warburg effect lactate aerobic glycolysis mitochondria oxidative stress ROS H2O2
shared by Nathan Goodyear on 11 Nov 14
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L-lactate functions as an onco-metabolite, stimulating mitochondrial biogenesis and OXPHOS in adjacent cancer cells, directly providing energy for tumor growth
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Oxidative stress in stromal fibroblasts then induces their metabolic conversion into cancer-associated fibroblasts. Such oxidative stress drives the onset of autophagy, mitophagy, and aerobic glycolysis in fibroblasts, resulting in the local production of high-energy mitochondrial fuels (such as L-lactate, ketone bodies, and glutamine). These recycled nutrients are then transferred to cancer cells, where they are efficiently burned via oxidative mitochondrial metabolism (OXPHOS)
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stromal L-lactate serves as a high-energy mitochondrial “fuel” for cancer cells. We have termed this new model of cancer metabolism “Two-Compartment Tumor Metabolism”, where two opposing metabolic compartments co-exist, side-by-side, with stromal glycolysis fueling OXPHOS in cancer cells
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Two-Compartment Tumor Metabolism
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Reverse Warburg Effect”, is that catabolic fibroblasts should promote tumor growth, without any increases in angiogenesis
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when cancer cells use L-lactate as a mitochondrial fuel source, this metabolic phenotype is a predictor of lethal cancer metabolism
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tumor microenvironment is intimately involved in tumor development and progression
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mitochondrial dysregulation is likely the “root cause” of several human disease(s), and especially epithelial cancers
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Both in vitro and in vivo studies have now provided convincing evidence that “activated” stromal fibroblasts, a.k.a., myofibroblasts, may play a critical role in initiating tumor recurrence, via paracrine interactions with adjacent tumor epithelial cells
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A new hypothesis is that cancer is not a cell autonomous disease, but rather a disease of the tumor microenvironment
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cancer cells behave as metabolic parasites, by inducing oxidative stress in adjacent normal fibroblasts
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recent experimental evidence indicates that cancer-associated fibroblasts have a catabolic phenotype, and undergo autophagy and mitophagy, resulting in the onset of glycolytic metabolism, driving L-lactate production, and its release into the tumor microenvironment
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oncogenic mutations in cancer cells lead to ROS production and the “secretion” of hydrogen peroxide species
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A good discussion of what is proposed the Reverse Warburg effect. A process by which the local environment dictates tumor progression. The cancer cells release ROS primarily in the form of H2O2 and this leads to Cancer Associated Fibroblasts (CAFs) in the stroma. The altered stromal environment increases ROS further and promotes ocogenic metabolites through the classic Warburg effect. This high lactate production from the CAFs then is used by the cancer cells via classic oxidative phosphorylation. Complex, beautiful and still an the understanding is a work in progress. This study/article points to the importance of oxidative stress in some cancer development through CAFs.
