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.