GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells
Radiotherapy is one of the conventional methods for the clinical treatment of breast cancer. However, radioresistance has an adverse effect on the prognosis of breast cancer patients after radiotherapy. In this study, using bioinformatic analysis of GSE59732 and GSE59733 datasets in the Gene Express...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10911 |
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| author | Xinrui Zhao Xinglong Liu Songling Hu Yan Pan Jianghong Zhang Guomei Tai Chunlin Shao |
| author_facet | Xinrui Zhao Xinglong Liu Songling Hu Yan Pan Jianghong Zhang Guomei Tai Chunlin Shao |
| author_sort | Xinrui Zhao |
| collection | DOAJ |
| description | Radiotherapy is one of the conventional methods for the clinical treatment of breast cancer. However, radioresistance has an adverse effect on the prognosis of breast cancer patients after radiotherapy. In this study, using bioinformatic analysis of GSE59732 and GSE59733 datasets in the Gene Expression Omnibus (GEO) database together with the prognosis database of breast cancer patients after radiotherapy, the <i>GDF15</i> gene was screened out to be related to the poor prognosis of breast cancer after radiotherapy. Compared with radiosensitive parental breast cancer cells, breast cancer cells with acquired radioresistance exhibited a high level of GDF15 expression and enhanced epithelial-to-mesenchymal transition (EMT) properties of migration and invasion, as well as obvious stem-like traits, including the increases of mammosphere formation ability, the proportion of stem cells (CD44<sup>+</sup> CD24<sup>−</sup> cells), and the expressions of stem cell-related markers (SOX2, NANOG). Moreover, knockdown of <i>GDF15</i> sensitized the radioresistance cells to irradiation and significantly inhibited their EMT and stem-like traits, indicating that GDF15 promoted the radioresistance of breast cancer by enhancing the properties of EMT and stemness. Conclusively, GDF15 may be applicable as a novel prognosis-related biomarker and a potential therapeutic target for breast cancer radiotherapy. |
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| format | Article |
| id | doaj.art-233373037156459282880b3c76e55a97 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:41:34Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-233373037156459282880b3c76e55a972023-11-23T16:50:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181091110.3390/ijms231810911GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer CellsXinrui Zhao0Xinglong Liu1Songling Hu2Yan Pan3Jianghong Zhang4Guomei Tai5Chunlin Shao6Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Radiotherapy, Nantong Tumor Hospital and the Affiliated Tumor Hospital of Nantong University, Nantong 226631, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaRadiotherapy is one of the conventional methods for the clinical treatment of breast cancer. However, radioresistance has an adverse effect on the prognosis of breast cancer patients after radiotherapy. In this study, using bioinformatic analysis of GSE59732 and GSE59733 datasets in the Gene Expression Omnibus (GEO) database together with the prognosis database of breast cancer patients after radiotherapy, the <i>GDF15</i> gene was screened out to be related to the poor prognosis of breast cancer after radiotherapy. Compared with radiosensitive parental breast cancer cells, breast cancer cells with acquired radioresistance exhibited a high level of GDF15 expression and enhanced epithelial-to-mesenchymal transition (EMT) properties of migration and invasion, as well as obvious stem-like traits, including the increases of mammosphere formation ability, the proportion of stem cells (CD44<sup>+</sup> CD24<sup>−</sup> cells), and the expressions of stem cell-related markers (SOX2, NANOG). Moreover, knockdown of <i>GDF15</i> sensitized the radioresistance cells to irradiation and significantly inhibited their EMT and stem-like traits, indicating that GDF15 promoted the radioresistance of breast cancer by enhancing the properties of EMT and stemness. Conclusively, GDF15 may be applicable as a novel prognosis-related biomarker and a potential therapeutic target for breast cancer radiotherapy.https://www.mdpi.com/1422-0067/23/18/10911bioinformatics analysisGDF15breast cancer cellsradioresistanceEMTstem-like traits |
| spellingShingle | Xinrui Zhao Xinglong Liu Songling Hu Yan Pan Jianghong Zhang Guomei Tai Chunlin Shao GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells International Journal of Molecular Sciences bioinformatics analysis GDF15 breast cancer cells radioresistance EMT stem-like traits |
| title | GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells |
| title_full | GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells |
| title_fullStr | GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells |
| title_full_unstemmed | GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells |
| title_short | GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells |
| title_sort | gdf15 contributes to radioresistance by mediating the emt and stemness of breast cancer cells |
| topic | bioinformatics analysis GDF15 breast cancer cells radioresistance EMT stem-like traits |
| url | https://www.mdpi.com/1422-0067/23/18/10911 |
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