ArticleCancer research2016
Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 56 citations in OpenAlex.
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Cancer stem cell plasticity in shaping drug resistance landscapes in prostate cancer.Journal of advanced research · 2026Review
- Role of PTK6 in the diagnosis, prognosis, and immune infiltration of pancreatic cancer based on evidence from bioinformatics analysis and experimental validation.Discover oncology · 2026Article
- An AIB1 isoform rewires glucocorticoid receptor signaling to promote TNBC progression.iScience · 2026Article
- Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy.Cancers · 2026Review
- Shared genetic architecture of psychoactive substance use and pan-cancer: insights from a large‑scale genome‑wide cross‑trait analysis.BMC medicine · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- The PELP1 Pathway and Its Importance in Cancer Treatment.Biomolecules · 2025Review
- Proline-, Glutamic Acid-, Leucine-Rich Protein 1 (PELP1): Diversity, Structural Conservation, and Evolutionary Origins Across the Species.International journal of molecular sciences · 2025Article
- Molecular mechanism of the crosstalk between glucocorticoid receptor (GR) and hypoxia-inducible factor 3α (HIF-3α) pathways.Marine life science & technology · 2025Article
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Glucocorticoid receptors orchestrate a convergence of host and cellular stress signals in triple negative breast cancer.The Journal of steroid biochemistry and molecular biology · 2024Review
- Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.Discover oncology · 2024Article
- Glucocorticoid receptor: a harmonizer of cellular plasticity in breast cancer-directs the road towards therapy resistance, metastatic progression and recurrence.Cancer metastasis reviews · 2024Review
- Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.Frontiers in immunology · 2024Review
- Prognostic impact of PTK6 expression in triple negative breast cancer.BMC women's health · 2023Article
- A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort.BMC cancer · 2023Article
- Glucocorticoid Receptor and Ovarian Cancer: From Biology to Therapeutic Intervention.Biomolecules · 2023Review
- The Role of Glucocorticoids in Breast Cancer Therapy.Current oncology (Toronto, Ont.) · 2022Review
- Mechanisms behind context-dependent role of glucocorticoids in breast cancer progression.Cancer metastasis reviews · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Cancer cells use stress response pathways to sustain their pathogenic behavior. In breast cancer, stress response-associated phenotypes are mediated by the breast tumor kinase, Brk (PTK6), via the hypoxia-inducible factors HIF-1α and HIF-2α. Given that glucocorticoid receptor (GR) is highly expressed in triple-negative breast cancer (TNBC), we investigated cross-talk between stress hormone-driven GR signaling and HIF-regulated physiologic stress. Primary TNBC tumor explants or cell lines treated with the GR ligand dexamethasone exhibited robust induction of Brk mRNA and protein that was HIF1/2-dependent. HIF and GR coassembled on the BRK promoter in response to either hypoxia or dexamethasone, indicating that Brk is a direct GR/HIF target. Notably, HIF-2α, not HIF-1α, expression was induced by GR signaling, and the important steroid receptor coactivator PELP1 was also found to be induced in a HIF-dependent manner. Mechanistic investigations showed how PELP1 interacted with GR to activate Brk expression and demonstrated that physiologic cell stress, including hypoxia, promoted phosphorylation of GR serine 134, initiating a feed-forward signaling loop that contributed significantly to Brk upregulation. Collectively, our findings linked cellular stress (HIF) and stress hormone (cortisol) signaling in TNBC, identifying the phospho-GR/HIF/PELP1 complex as a potential therapeutic target to limit Brk-driven progression and metastasis in TNBC patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.