Glucocorticoid-Induced Proteome and Phosphoproteome Changes in Breast Cancer Cell Lines

Glucocorticoids (GCs) are steroid hormones that bind to the glucocorticoid receptor (GR) as ligands to initiate systemic anti-inflammatory effects. GCs are commonly administered alongside chemotherapy to reduce treatment-related side effects in breast cancer patients. However, GC administration has been shown to promote metastasis in breast cancer. In this study, we used quantitative mass-spectrometry-based approaches to analyze proteome and phosphoproteome of three breast cancer cell lines following treatment of a clinically approved synthetic GC, dexamethasone (Dex). By comparing MCF7, MDA-MB-231, and MDA-MB-436 cells, we suggest that the level of GR significantly affects Dex-mediated responses. Additionally, we identify noncanonical transcription factors (TFs) and kinases that are regulated by GR in different cell lines. Together, our data present Dex-induced protein modulations and modifications involving several TFs and kinases that regulate cytoskeletal remodeling and migration in breast cancer cell lines. These findings highlight the need for careful consideration of GC use in breast cancer therapy and identify potential molecular targets for mitigating adverse effects.