(Open access funding provided by Semmelweis University)
The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour,
although data on its effects are conflicting. The impact of GR agonist dexamethasone
(dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative
(TN) breast cancer cell lines in both 2D and 3D cultures was studied using multiple
in vitro functional assays and transcriptome sequencing. GR activation increased cell
motility in TN but not in ER + tumour cells, as observed in both collective and single-cell
migration tests. Time-lapse analysis showed enhanced motility after 4-6 h in wound
healing, despite dex inhibiting migration initially. This inhibition was observed
at 2 h in single-cell tracking migration assays. Cell proliferation increased in TN
and decreased in ER + cells upon GR activation, reversed by GR antagonist. RNA sequencing
revealed dex's impact on cell adhesion and extracellular matrix signalling in TN cells
and on DNA replication in ER + cells. Based on data from 1085 human breast cancer
specimens, GR pathway expression correlated with migratory, extracellular matrix,
and angiogenesis gene signatures. Additionally, higher expression of GR and increased
GR signature were observed in fast-migrating cells compared to slow-migrating ones.
Positive correlation between the GR signature and migration signature at the single-cell
level indicated an association between GR activity and cell migration. For the first
time, we assessed altered time-lapse migration dynamics in TN breast cancer cells,
potentially contributing to cancer progression and prognosis, highlighting that the
effects of dexamethasone on breast cancer cell migration are influenced by ER status
and treatment duration.
