Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties
The Wnt pathway is integrally involved in regulating self-renewal, proliferation, and maintenance of cancer stem cells (CSCs). We explored the effect of the Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), in modulating epithelial to mesenchymal transition (EMT) in CSCs from human gliobl...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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Public Library of Science
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/44633 |
| _version_ | 1848757057174372352 |
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| author | Bhuvanalakshmi, G. Arfuso, Frank Millward, M. Dharmarajan, Arunasalam Warrier, Sudha |
| author_facet | Bhuvanalakshmi, G. Arfuso, Frank Millward, M. Dharmarajan, Arunasalam Warrier, Sudha |
| author_sort | Bhuvanalakshmi, G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The Wnt pathway is integrally involved in regulating self-renewal, proliferation, and maintenance of cancer stem cells (CSCs). We explored the effect of the Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), in modulating epithelial to mesenchymal transition (EMT) in CSCs from human glioblastoma cells lines, U87 and U373. sFRP4 chemo-sensitized CSC-enriched cells to the most commonly used anti-glioblastoma drug, temozolomide (TMZ), by the reversal of EMT. Cell movement, colony formation, and invasion in vitro were suppressed by sFRP4+TMZ treatment, which correlated with the switch of expression of markers from mesenchymal (Twist, Snail, N-cadherin) to epithelial (E-cadherin). sFRP4 treatment elicited activation of the +2 pathway, which antagonizes the Wnt/ß-catenin pathway. Significantly, the chemo-sensitization effect of sFRP4 was correlated with the reduction in the expression of drug resistance markers ABCG2, ABCC2, and ABCC4. The efficacy of sFRP4+TMZ treatment was demonstrated in vivo using nude mice, which showed minimum tumor engraftment using CSCs pretreated with sFRP4+TMZ. These studies indicate that sFRP4 treatment would help to improve response to commonly used chemotherapeutics in gliomas by modulating EMT via the Wnt/ß-catenin pathway. These findings could be exploited for designing better targeted strategies to improve chemo-response and eventually eliminate glioblastoma CSCs. |
| first_indexed | 2025-11-14T09:22:02Z |
| format | Journal Article |
| id | curtin-20.500.11937-44633 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:22:02Z |
| publishDate | 2015 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-446332017-09-13T14:11:36Z Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties Bhuvanalakshmi, G. Arfuso, Frank Millward, M. Dharmarajan, Arunasalam Warrier, Sudha The Wnt pathway is integrally involved in regulating self-renewal, proliferation, and maintenance of cancer stem cells (CSCs). We explored the effect of the Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), in modulating epithelial to mesenchymal transition (EMT) in CSCs from human glioblastoma cells lines, U87 and U373. sFRP4 chemo-sensitized CSC-enriched cells to the most commonly used anti-glioblastoma drug, temozolomide (TMZ), by the reversal of EMT. Cell movement, colony formation, and invasion in vitro were suppressed by sFRP4+TMZ treatment, which correlated with the switch of expression of markers from mesenchymal (Twist, Snail, N-cadherin) to epithelial (E-cadherin). sFRP4 treatment elicited activation of the +2 pathway, which antagonizes the Wnt/ß-catenin pathway. Significantly, the chemo-sensitization effect of sFRP4 was correlated with the reduction in the expression of drug resistance markers ABCG2, ABCC2, and ABCC4. The efficacy of sFRP4+TMZ treatment was demonstrated in vivo using nude mice, which showed minimum tumor engraftment using CSCs pretreated with sFRP4+TMZ. These studies indicate that sFRP4 treatment would help to improve response to commonly used chemotherapeutics in gliomas by modulating EMT via the Wnt/ß-catenin pathway. These findings could be exploited for designing better targeted strategies to improve chemo-response and eventually eliminate glioblastoma CSCs. 2015 Journal Article http://hdl.handle.net/20.500.11937/44633 10.1371/journal.pone.0127517 Public Library of Science unknown |
| spellingShingle | Bhuvanalakshmi, G. Arfuso, Frank Millward, M. Dharmarajan, Arunasalam Warrier, Sudha Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| title | Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| title_full | Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| title_fullStr | Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| title_full_unstemmed | Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| title_short | Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| title_sort | secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties |
| url | http://hdl.handle.net/20.500.11937/44633 |