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 Expression Omnibus (GEO) database together with the prognosis database of breast cancer patients after radiotherapy, the GDF15 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(+) CD24(-) cells), and the expressions of stem cell-related markers (SOX2, NANOG). Moreover, knockdown of GDF15 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.

Automated summary

Radiotherapy is a conventional treatment method for breast cancer, but radioresistance affects the prognosis negatively. This study found that the GDF15 gene is related to poor prognosis in breast cancer patients after radiotherapy. Breast cancer cells with acquired radioresistance showed high expression of GDF15 and enhanced properties of epithelial-to-mesenchymal transition (EMT) and stemness. Knockdown of GDF15 sensitized radioresistant cells to irradiation and inhibited their EMT and stemness properties. GDF15 may serve as a prognosis-related biomarker and a potential therapeutic target for breast cancer radiotherapy.