Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma
MetadataShow full item record
Aim: Epithelial-mesenchymal transition (EMT) is characterized by the acquisition of invasive fibroblast-like morphology by epithelial cells that are highly polarized. EMT is recognized as a crucial mechanism in cancer progression and metastasis. In this study, we sought to assess the involvement of manganese superoxide dismutase (MnSOD) during the switch between epithelial-like and mesenchymal-like phenotypes in breast carcinoma. Results: Analysis of breast carcinomas from The Cancer Genome Atlas database revealed strong positive correlation between tumors' EMT score and the expression of MnSOD. This positive correlation between MnSOD and EMT score was significant and consistent across all breast cancer subtypes. Similarly, a positive correlation of EMT score and MnSOD expression was observed in established cell lines derived from breast cancers exhibiting phenotypes ranging from the most epithelial to the most mesenchymal. Interestingly, using phenotypically distinct breast cancer cell lines, we provide evidence that constitutively high or induced expression of MnSOD promotes the EMT-like phenotype by way of a redox milieu predominantly driven by hydrogen peroxide (H2O2). Conversely, gene knockdown of MnSOD results in the reversal of EMT to a mesenchymal-epithelial transition (MET)-like program, which appears to be a function of superoxide (O2-•)-directed signaling. Innovation and Conclusion: These data underscore the involvement of MnSOD in regulating the switch between the EMT and MET-associated phenotype by influencing cellular redox environment via its effect on the intracellular ratio between O2-• and H2O2. Strategies to manipulate MnSOD expression and/or the cellular redox milieu vis-a-vis O2-•:H2O2 could have potential therapeutic implications.
Showing items related by title, author, creator and subject.
Thirunavukkarasan, M.; Wang, C.; Rao, A.; Hind, T.; Teo, Y.; Siddiquee, A.; Goghari, M.; Kumar, Alan Prem; Herr, D. (2017)Short chain fatty acids (2 to 6 carbons in length) are ubiquitous lipids that are present in human plasma at micromolar concentrations. In addition to serving as metabolic precursors for lipid and carbohydrate synthesis, ...
Breast cancer stem-like cells are inhibited by diosgenin, a steroidal saponin, by the attenuation of the Wnt ß-catenin signaling via the Wnt antagonist secreted frizzled related protein-4Bhuvanalakshmi, G.; Basappa; Rangappa, K.; Dharmarajan, Arunasalam; Sethi, Gautam; Kumar, Alan Prem; Warrier, Sudha (2017)Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of ...
Schwab, R.; Amin, N.; Flanagan, D.; Johanson, T.; Phesse, T.; Vincan, Elizabeth (2017)Background: Metastasis underlies most colorectal cancer mortality. Cancer cells spread through the body as single cells or small clusters of cells that have an invasive, mesenchymal, nonproliferative phenotype. At the ...