ArticleMolecular cancer2018
AR-PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer.
Article in Molecular cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Target Attainment and Clinical and Biochemical Parameters Associated with the Pharmacokinetics of 12 Tyrosine Kinase Inhibitors.Clinical pharmacokinetics · 2026Article
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Molecular convergence of luminal androgen receptor and molecular apocrine defines a distinct entity in ER-negative breast tumors.Breast cancer research : BCR · 2025Article
- Androgen receptor interacts with c-Myc to regulate macrophage-osteoclast axis and drive bone metastasis in triple negative breast cancer.British journal of cancer · 2025Article
- TRMT10A regulates tRNA-ArgCCT mCell death & disease · 2025Article
- Identifying aging-related biomarkers in adipose tissue using integrative bioinformatics and machine-learning approaches: discovery of ELN, MXD1, and FGF21 as key genes.Frontiers in endocrinology · 2025Article
- MAD1 deficiency accelerates hepatocellular proliferation via suppressing TGF-β signaling.Heliyon · 2024Article
- SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer.Cell death & disease · 2023Article
- Nuclear transport maintenance of USP22-AR by Importin-7 promotes breast cancer progression.Cell death discovery · 2023Article
- HOXA5 inhibits the proliferation of extrahepatic cholangiocarcinoma cells by enhancing MXD1 expression and activating the p53 pathway.Cell death & disease · 2022Article
- The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance.Journal of cellular and molecular medicine · 2021Article
- Medulloblastoma recurrence and metastatic spread are independent of colony-stimulating factor 1 receptor signaling and macrophage survival.Journal of neuro-oncology · 2021Article
- Triple-negative breast cancer: new treatment strategies in the era of precision medicine.Science China. Life sciences · 2021Review
- RING-finger protein 6 enhances c-Myc-mediated Warburg effect by promoting MAD1 degradation to facilitate pancreatic cancer metastasis.American journal of cancer research · 2021Article
- The expression and prognostic role of EBP1 and relationship with AR in HER2+ breast cancer.Virchows Archiv : an international journal of pathology · 2020Article
- Triple negative breast cancer: special histological types and emerging therapeutic methods.Cancer biology & medicine · 2020Review
- Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c-MYC axis in breast cancer.Journal of cellular and molecular medicine · 2020Article
- Double Agent:Cancer management and research · 2020Review
- β-Catenin nuclear localization positively feeds back on EGF/EGFR-attenuated AJAP1 expression in breast cancer.Journal of experimental & clinical cancer research : CR · 2019Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAndrogen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear.
methodsAR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR-PDEF-MAD1-MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo.
resultsWe found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo.
conclusionsOur data highlight the role of the AR-PDEF-MAD1-MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC.
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