ArticleOncotarget2017
MED15 overexpression in prostate cancer arises during androgen deprivation therapy via PI3K/mTOR signaling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Emerging roles of pseudogene-derived lncRNAs in cancer stem cells: Non-coding clues and therapeutic targets in cancer medicine.Genes & diseases · 2026Review
- Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.Open biology · 2024Article
- MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis.Cell death discovery · 2024Article
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- Driver gene detection through Bayesian network integration of mutation and expression profiles.Bioinformatics (Oxford, England) · 2022Article
- Step-by-Step Construction of Gene Co-Expression Network Analysis for Identifying Novel Biomarkers of Sepsis Occurrence and Progression.International journal of general medicine · 2021Article
- Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.Molecular biology reports · 2020Review
- MED15, transforming growth factor beta 1 (TGF-β1), FcγRIII (CD16), and HNK-1 (CD57) are prognostic biomarkers of oral squamous cell carcinoma.Scientific reports · 2020Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- A Rare Partner of TFE3 in the Xp11 Translocation Renal Cell Carcinoma: Clinicopathological Analyses and Detection of MED15-TFE3 Fusion.BioMed research international · 2019Article
- The knockdown of the Mediator complex subunit MED15 restrains urothelial bladder cancer cells' malignancy.Oncology letters · 2018Article
- Review
- Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma.Oncology letters · 2018Article
- The Mediator complex subunit MED15, a promoter of tumour progression and metastatic spread in renal cell carcinoma.Cancer biomarkers : section A of Disease markers · 2018Article
- Molecular mechanisms of therapy resistance in solid tumors: chasing "moving" targets.Virchows Archiv : an international journal of pathology · 2017Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Androgen deprivation therapy (ADT) is the main therapeutic option for advanced prostate cancer (PCa). After initial regression, most tumors develop into castration-resistant PCa (CRPC). Previously, we found the Mediator complex subunit MED15 to be overexpressed in CRPC and to correlate with clinical outcome. Therefore, we investigated whether MED15 is implicated in the signaling changes taking place during progression to CRPC. Immunohistochemistry (IHC) for MED15 on matched samples from the same patients before and after ADT reveals significantly increased MED15 expression after ADT in 72%. A validation cohort comprising samples before and after therapy confirmed our observations. Protein analysis for pAKT and pSMAD3 shows that MED15 correlates with PI3K and TGFß activities, respectively, and that hyper-activation of both pathways simultaneously correlates with highest levels of MED15. We further show that MED15 protein expression increases in LNCaP cells under androgen deprivation, and via EGF mediated PI3K activation. PI3K/mTOR and TGFß-receptor inhibition results in decreased MED15 expression. MED15 knockdown reduces LNCaP cell viability and induces apoptosis during androgen deprivation, while cell cycle is not affected. Collectively, MED15 overexpression arises during ADT via hyper-activation of PI3K/mTOR signaling, thus MED15 may serve as a predictive marker for response to PI3K/mTOR inhibitors. Furthermore, MED15 is potentially a therapeutic target for the treatment of CRPC.
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