Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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Mary Ann Liebert, Inc. Publishers
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/51158 |
| _version_ | 1848758629820268544 |
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| author | Loo, S. Hirpara, J. Pandey, V. Tan, T. Yap, C. Lobie, P. Thiery, J. Goh, B. Pervaiz, Shazib Clément, M. Kumar, Alan Prem |
| author_facet | Loo, S. Hirpara, J. Pandey, V. Tan, T. Yap, C. Lobie, P. Thiery, J. Goh, B. Pervaiz, Shazib Clément, M. Kumar, Alan Prem |
| author_sort | Loo, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T09:47:02Z |
| format | Journal Article |
| id | curtin-20.500.11937-51158 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:47:02Z |
| publishDate | 2016 |
| publisher | Mary Ann Liebert, Inc. Publishers |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-511582018-03-29T09:09:26Z Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma Loo, S. Hirpara, J. Pandey, V. Tan, T. Yap, C. Lobie, P. Thiery, J. Goh, B. Pervaiz, Shazib Clément, M. Kumar, Alan Prem 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. 2016 Journal Article http://hdl.handle.net/20.500.11937/51158 10.1089/ars.2015.6524 Mary Ann Liebert, Inc. Publishers restricted |
| spellingShingle | Loo, S. Hirpara, J. Pandey, V. Tan, T. Yap, C. Lobie, P. Thiery, J. Goh, B. Pervaiz, Shazib Clément, M. Kumar, Alan Prem Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma |
| title | Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma |
| title_full | Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma |
| title_fullStr | Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma |
| title_full_unstemmed | Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma |
| title_short | Manganese Superoxide Dismutase Expression Regulates the Switch between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma |
| title_sort | manganese superoxide dismutase expression regulates the switch between an epithelial and a mesenchymal-like phenotype in breast carcinoma |
| url | http://hdl.handle.net/20.500.11937/51158 |