GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells.

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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.", "claims": [{"id": "claim-method", "statement": "A Student’s t-test was performed to compare the difference of independent groups, and the significant level was considered at p < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36142823", "locator": "sections[26] \"4.16. 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Moreover, knockdown of GDF15 sensitized the radioresistance cell"], "order_basis": "paper_text_order:1030", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["10% FBS and 1% penicillin/streptomycin. All cell lines were maintained in a humidified atmosphere containing 5% CO2", "d, NY, USA). MCF-7 and MDA-MB-231 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) su", "treptomycin. T-47D and MDA-MB-468 cells were cultured in RPMI-1640 medium containing 10% FBS and 1% p", "above 585 DEGs. (C) Venn diagrams of DEGs in MCF-7 and ZR751 cell lines from GSE59732 dataset a"], "order_basis": "paper_text_order:2951", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["dividual cancer stages of breast cancer. (G) Western blot assay of the GDF15 protein expression in MCF", "7D, MDA-MB-23, MDA-MB-468). 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