ArticleCancer biology & therapy2015
Inhibition of SGK1 enhances mAR-induced apoptosis in MCF-7 breast cancer cells.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Androgens Modulate Bcl-2 Agonist of Cell Death (BAD) Expression and Function in Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Review
- Induction of SGK1 via glucocorticoid-influenced clinical outcome of triple-negative breast cancer patients.Breast cancer research and treatment · 2023Article
- SGK1 in Cancer: Biomarker and Drug Target.Cancers · 2022Article
- SGK1 mutation status can further stratify patients with germinal center B-cell-like diffuse large B-cell lymphoma into different prognostic subgroups.Cancer medicine · 2022Article
- Rewiring of the Endocrine Network in Triple-Negative Breast Cancer.Frontiers in oncology · 2022Review
- NGF-Induced Nav1.7 Upregulation Contributes to Chronic Post-surgical Pain by Activating SGK1-Dependent Nedd4-2 Phosphorylation.Molecular neurobiology · 2021Article
- The histone demethylase KDM2B activates FAK and PI3K that control tumor cell motility.Cancer biology & therapy · 2020Article
- SGK1 in Human Cancer: Emerging Roles and Mechanisms.Frontiers in oncology · 2020Review
- The prospect of serum and glucocorticoid-inducible kinase 1 (SGK1) in cancer therapy: a rising star.Therapeutic advances in medical oncology · 2020Review
- SGK1 protein expression is a prognostic factor of lung adenocarcinoma that regulates cell proliferation and survival.International journal of clinical and experimental pathology · 2019Article
- Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis.International journal of molecular sciences · 2016Review
- Article
- Article
- Up-regulation of Orai1 expression and store operated Ca(2+) entry following activation of membrane androgen receptors in MCF-7 breast tumor cells.BMC cancer · 2015Article
- Preclinical model in HCC: the SGK1 kinase inhibitor SI113 blocks tumor progression in vitro and in vivo and synergizes with radiotherapy.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional membrane androgen receptors (mAR) have previously been described in MCF-7 breast cancer cells. Their stimulation by specific testosterone albumin conjugates (TAC) activate rapidly non-genomic FAK/PI3K/Rac1/Cdc42 signaling, trigger actin reorganization and inhibit cell motility. PI3K stimulates serum and glucocorticoid inducible kinase SGK1, which in turn regulates the function of mAR. In the present study we addressed the role of SGK1 in mAR-induced apoptosis. TAC-stimulated mAR activation elicited apoptosis of MCF-7 cells, an effect significantly potentiated by concomitant incubation of the cells with TAC and the specific SGK1 inhibitors EMD638683 and GSK650394. In line with this, TAC and EMD638683 activated caspase-3. These effects were insensitive to the classical androgen receptor (iAR) antagonist flutamide, pointing to iAR-independent, mAR-induced responses. mAR activation and SGK1 inhibition further considerably augmented the radiation-induced apoptosis of MCF-7 cells. Moreover, TAC- and EMD638683 triggered early actin polymerization in MCF-7 cells. Blocking actin restructuring with cytochalasin B abrogated the TAC- and EMD638683-induced pro-apoptotic responses. Further analysis of the molecular signaling revealed late de-phosphorylation of FAK and Akt. Our results demonstrate that mAR activation triggers pro-apoptotic responses in breast tumor cells, an effect significantly enhanced by SGK1 inhibition, involving actin reorganization and paralleled by down-regulation of FAK/Akt signaling.
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