Glucocorticoid-induced proteome and phosphoproteome changes in breast cancer cell lines

Abstract

Glucocorticoids (GCs) are steroid hormones that bind to 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 GC treatments. By comparing MCF7, MDA-MB-231, and MDA-MB-436 cells, we suggest that the level of GR significantly affects GC-mediated responses. Additionally, we identify noncanonical transcription factors (TFs) and kinases that are regulated by GCs in different cell lines. Together, our data present GC-induced modulations and modifications at protein level, indicating that breast cancer metastasis occurs via TF- and kinase-dependent signaling pathways. These findings highlight the need for careful consideration of GC use in breast cancer therapy and identify potential molecular targets for mitigating adverse effects. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/690354v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1c9ff8borg.highwire.dtl.DTLVardef@a8172forg.highwire.dtl.DTLVardef@18a4b85org.highwire.dtl.DTLVardef@6413cf_HPS_FORMAT_FIGEXP M_FIG C_FIG