ROS Links Glucose Metabolism to Breast Cancer Stem Cell and EMT Phenotype

Abstract

Cancer stem cells display an epithelial-mesenchymal transition phenotype and are resistant to current therapies. In this issue of Cancer Cell, Dong and colleagues demonstrate that these phenotypes in basal-like breast cancer are promoted by a metabolic switch to glucose metabolism, resulting in decreased reactive oxygen species levels.

Reactive oxygen species induce MMP12‐dependent degradation of collagen 5 and fibronectin to promote the motility of human umbilical cord‐derived mesenchymal stem cells

“…Similar results have been observed in bone marrow MSCs and in breast cancer stem cells (Li et al, 2009;Schieber and Chandel, 2013). In addition, UCB-MSCs treated with H2O2 have the ability to enhance epidermal reorganization, restoring the normal wound microarchitecture almost completely.…”

Genetics and metabolic deregulation following cancer initiation: A world to explore

“…ROS-mediated STAT3 activation lead to MAPK and PI3K (phosphoinositide-3-kinase) activation [110], inducing SNAIL expression [111]. SNAIL interacts to G9a, a H3K9me2-responsive methyltransferase and recruits DNA methyltransferases to E-cadherin promoter [112]. The zinc-fingers of SNAIL can also bind to E-box motif (5 0 -CANNTG-3 0 ) present in target genes [111].…”

Metabolic control of cancer cell stemness: Lessons from iPS cells

“…Accordingly, an increased reliance on glucose metabolism reduces the levels of ROS to promote EMT and CSC-like phenotypes. 61,62 While the ratio of reduced glutathione (GSH), the primary intracellular antioxidant, to oxidized (GSSH) glutathione decreases, as does the level of NADH, during stem cell differentiation, CSC possess enhanced mechanisms of protection from stress induced by ROS that might render them resistant to chemo-and radiotherapy through an upregulation of GSH synthesis. [76][77][78] Consequently, new strategies aimed to induce ROS via depletion of cellular glutathione can be viewed as promising therapeutic approaches against CSC.…”

“…Accordingly, recent studies have confirmed that a metabolic switch to glucose metabolism is a critical promotional event in the epithelial-tomesenchymal (EMT)-driven CSC-like phenotype. 61,62 Epigenetic silencing of the gluconeogenic enzyme fructose-1,6-biphosphate, which catalyzes the energyconsuming conversion of fructose 1,6-biphosphate to fructose-6-phosphate, is employed by CSC as a mechanism of glucose flux maintenance via glycolysis and other associated biosynthetic pathways.…”