Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression.

摘要: Epithelial-mesenchymal transition (EMT) promotes cancer cell invasion, metastasis and treatment failure. EMT may be activated in cells by reactive oxygen species (ROS). promote conversion of a subset from CD44(low)-CD24(high) (CD44L) epithelial phenotype to CD44(high)-CD24(-/low) (CD44H) mesenchymal phenotype, the latter associated with increased malignant properties cells. ROS are required for undergoing EMT, although excessive induce death or senescence; however, little is known as how cellular antioxidant capabilities regulated during EMT. Mitochondrial superoxide dismutase 2 (SOD2) frequently overexpressed oral esophageal cancers. Here, we investigate mechanisms SOD2 transcriptional regulation well functional role this Using well-characterized genetically engineered human lines coupled RNA interference flow cytometric approaches, find that transforming growth factor (TGF)-β stimulates resulting CD44L CD44H cells, which display upregulation. induction transformed keratinocytes was concurrent suppression TGF-β-mediated both senescence. gene expression appeared transcriptionally NF-κB ZEB2, but not ZEB1. Moreover, SOD2-mediated activity restrict at early stages These data provide novel mechanistic insights into dynamic In addition, delineate via influence upon distinct subsets have been implicated tumor biology.