ArticleOncogene2020
Targeting MEK5 impairs nonhomologous end-joining repair and sensitizes prostate cancer to DNA damaging agents.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma.International journal of biological sciences · 2026Article
- Multifaceted role of nitric oxide in vascular dementia.Medical gas research · 2025Review
- Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma.Blood advances · 2025Article
- Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation.Cancer metastasis reviews · 2024Review
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Review
- P38 MAPK and Radiotherapy: Foes or Friends?Cancers · 2023Review
- Multifaceted regulation and functions of 53BP1 in NHEJ‑mediated DSB repair (Review).International journal of molecular medicine · 2022Review
- DNA damage repair-related gene signature predicts prognosis and indicates immune cell infiltration landscape in skin cutaneous melanoma.Frontiers in endocrinology · 2022Article
- FOXP1 and NDRG1 act differentially as downstream effectors of RAD9-mediated prostate cancer cell functions.Cellular signalling · 2021Article
- Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma.Cancers · 2021Article
- The Clinical Significance of DNA Damage Repair Signatures in Clear Cell Renal Cell Carcinoma.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Radiotherapy is commonly used to treat a variety of solid human tumors, including localized prostate cancer. However, treatment failure often ensues due to tumor intrinsic or acquired radioresistance. Here we find that the MEK5/ERK5 signaling pathway is associated with resistance to genotoxic stress in aggressive prostate cancer cells. MEK5 knockdown by RNA interference sensitizes prostate cancer cells to ionizing radiation (IR) and etoposide treatment, as assessed by clonogenic survival and short-term proliferation assays. Mechanistically, MEK5 downregulation impairs phosphorylation of the catalytic subunit of DNA-PK at serine 2056 in response to IR or etoposide treatment. Although MEK5 knockdown does not influence the initial appearance of radiation- and etoposide-induced γH2AX and 53BP1 foci, it markedly delays their resolution, indicating a DNA repair defect. A cell-based assay shows that nonhomologous end joining (NHEJ) is compromised in cells with ablated MEK5 protein expression. Finally, MEK5 silencing combined with focal irradiation causes strong inhibition of tumor growth in mouse xenografts, compared with MEK5 depletion or radiation alone. These findings reveal a convergence between MEK5 signaling and DNA repair by NHEJ in conferring resistance to genotoxic stress in advanced prostate cancer and suggest targeting MEK5 as an effective therapeutic intervention in the management of this disease.
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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.