Abstract
Purpose
Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive breast malignancy. Glucocorticoid (GC)–glucocorticoid receptor (GR) pathway plays a pivotal role in the cellular responses to various stresses including chemotherapy. Serum- and glucocorticoid-induced kinase-1 (SGK1) is known as an important downstream effector molecule in the GR signaling pathway, we attempted to explore its clinicopathological and functional significance in TNBC in which GR is expressed.
Methods
We first immunolocalized GR and SGK1 and correlated the results with clinicopathological variables and clinical outcome in 131 TNBC patients. We also evaluated the effects of SGK1 on the cell proliferation and migration in TNBC cell lines with administration of dexamethasone (DEX) to further clarify the significance of SGK1.
Results
The status of SGK1 in carcinoma cells was significantly associated with adverse clinical outcome in TNBC patients examined and was significantly associated with lymph node metastasis, pathological stage, and lymphatic invasion of the patients. In particular, SGK1 immunoreactivity was significantly associated with an increased risk of recurrence in GR-positive TNBC patients. Subsequent in vitro studies also demonstrated that DEX promoted TNBC cell migration and the silencing of gene expression did inhibit the cell proliferation and migration of TNBC cells under DEX treatment.
Conclusions
To the best of our knowledge, this is the first study to explore an association between SGK1 and clinicopathological variables and clinical outcome of TNBC patients. SGK1 status was significantly positively correlated with adverse clinical outcome of TNBC patients and promoted carcinoma cell proliferation and migration of carcinoma cells.
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Data Availability
The datasets used and/or analyzed in the present study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank the members of the Department of Pathology and the Department of Breast and Endocrine Surgical Oncology in Tohoku University Graduate School of Medicine for their support.
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Zhang, J., Miki, Y., Iwabuchi, E. et al. Induction of SGK1 via glucocorticoid-influenced clinical outcome of triple-negative breast cancer patients. Breast Cancer Res Treat 200, 323–335 (2023). https://doi.org/10.1007/s10549-023-06990-4
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DOI: https://doi.org/10.1007/s10549-023-06990-4