The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b
Abstract Metastasis is the main cause of death in cancer patients, including breast cancer (BC). Despite recent progress in understanding the biological and molecular determinants of BC metastasis, effective therapeutic treatments are yet to be developed. Among the multitude of molecular mechanisms...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25373-0 |
| _version_ | 1818754208223985664 |
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| author | Khalid Sossey-Alaoui Elzbieta Pluskota Dorota Szpak William P. Schiemann Edward F. Plow |
| author_facet | Khalid Sossey-Alaoui Elzbieta Pluskota Dorota Szpak William P. Schiemann Edward F. Plow |
| author_sort | Khalid Sossey-Alaoui |
| collection | DOAJ |
| description | Abstract Metastasis is the main cause of death in cancer patients, including breast cancer (BC). Despite recent progress in understanding the biological and molecular determinants of BC metastasis, effective therapeutic treatments are yet to be developed. Among the multitude of molecular mechanisms that regulate cancer metastasis, the epithelial-to-mesenchymal transition (EMT) program plays a key role in the activation of the biological steps leading to the metastatic phenotype. Kindlin-2 has been associated with the pathogenesis of several types of cancers, including BC. The role of Kindlin-2 in the regulation of BC metastasis, and to a lesser extent in EMT is not well understood. In this study, we show that Kindlin-2 is closely associated with the development of the metastatic phenotype in BC. We report that knockout of Kindlin-2 in either human or mouse BC cells, significantly inhibits metastasis in both human and mouse models of BC metastasis. We also report that the Kindlin-2-mediated inhibition of metastasis is the result of inhibition of expression of key molecular markers of the EMT program. Mechanistically, we show that miR-200b, a master regulator of EMT, directly targets and inhibits the expression of Kindlin-2, leading to the subsequent inhibition of EMT and metastasis. Together, our data support the targeting of Kindlin-2 as a therapeutic strategy against BC metastasis. |
| first_indexed | 2024-12-18T05:19:36Z |
| format | Article |
| id | doaj.art-d9e7d9b1f90f44759827faaae4b78ccd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:19:36Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d9e7d9b1f90f44759827faaae4b78ccd2022-12-21T21:19:41ZengNature PortfolioScientific Reports2045-23222018-05-018111310.1038/s41598-018-25373-0The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200bKhalid Sossey-Alaoui0Elzbieta Pluskota1Dorota Szpak2William P. Schiemann3Edward F. Plow4Department of Molecular Cardiology, Lerner Research Institute, Cleveland ClinicDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland ClinicDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland ClinicCase Comprehensive Cancer CenterDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland ClinicAbstract Metastasis is the main cause of death in cancer patients, including breast cancer (BC). Despite recent progress in understanding the biological and molecular determinants of BC metastasis, effective therapeutic treatments are yet to be developed. Among the multitude of molecular mechanisms that regulate cancer metastasis, the epithelial-to-mesenchymal transition (EMT) program plays a key role in the activation of the biological steps leading to the metastatic phenotype. Kindlin-2 has been associated with the pathogenesis of several types of cancers, including BC. The role of Kindlin-2 in the regulation of BC metastasis, and to a lesser extent in EMT is not well understood. In this study, we show that Kindlin-2 is closely associated with the development of the metastatic phenotype in BC. We report that knockout of Kindlin-2 in either human or mouse BC cells, significantly inhibits metastasis in both human and mouse models of BC metastasis. We also report that the Kindlin-2-mediated inhibition of metastasis is the result of inhibition of expression of key molecular markers of the EMT program. Mechanistically, we show that miR-200b, a master regulator of EMT, directly targets and inhibits the expression of Kindlin-2, leading to the subsequent inhibition of EMT and metastasis. Together, our data support the targeting of Kindlin-2 as a therapeutic strategy against BC metastasis.https://doi.org/10.1038/s41598-018-25373-0 |
| spellingShingle | Khalid Sossey-Alaoui Elzbieta Pluskota Dorota Szpak William P. Schiemann Edward F. Plow The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b Scientific Reports |
| title | The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b |
| title_full | The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b |
| title_fullStr | The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b |
| title_full_unstemmed | The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b |
| title_short | The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b |
| title_sort | kindlin 2 regulation of epithelial to mesenchymal transition in breast cancer metastasis is mediated through mir 200b |
| url | https://doi.org/10.1038/s41598-018-25373-0 |
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