ArticleOncotarget2016
MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Palbociclib targets β-catenin for degradation and synergizes with KRAS or ERK5 inhibition in colorectal cancer preclinical models.Journal of translational medicine · 2026Article
- A different MAPK, ERK5 plays a critical role in cell specification and differentiation.Biochemistry and biophysics reports · 2026Review
- MicroRNA-873 Suppresses Viability and Invasion of Colorectal Cancer Through KRAS/MAPK Signaling and Sensitizes Tumor Spheroids to 5-Fluorouracil in a 3D Microwell Model.IEEE open journal of engineering in medicine and biology · 2026Article
- Dichloroacetate enhances Chemo-sensitivity in wild-type P53 breast cancer cells by modulating ABCG2 and NKG2DL.Scientific reports · 2025Article
- Toxic effects of Helix aspersa snail egg hydrolyzates obtained by static in vitro digestion on Caco-2 colorectal adenocarcinoma cells.Scientific reports · 2025Article
- Article
- 4-O-Methylascochlorin Synergistically Enhances 5-Fluorouracil-Induced Apoptosis by Inhibiting the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer Cells.International journal of molecular sciences · 2024Article
- MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.Cell death & disease · 2023Article
- Functional Analysis and Clinical Importance of ATP1A1 in Colon Cancer.Annals of surgical oncology · 2023Article
- Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications.Experimental & molecular medicine · 2023Article
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells.Cancer research communications · 2023Article
- Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation.Journal of cancer research and clinical oncology · 2022Article
- Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney.AAPS PharmSciTech · 2022Article
- The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.Cellular and molecular life sciences : CMLS · 2022Article
- BAY-885, a mitogen-activated protein kinase kinase 5 inhibitor, induces apoptosis by regulating the endoplasmic reticulum stress/Mcl-1/Bim pathway in breast cancer cells.Bioengineered · 2022Article
- Review
- ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled?Frontiers in cell and developmental biology · 2022Review
- Constitutive activation of MEK5 promotes a mesenchymal and migratory cell phenotype in triple negative breast cancer.Oncoscience · 2021Article
- Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MEK5/ERK5 signaling pathway is emerging as an important contributor to colon cancer onset, progression and metastasis; however, its relevance to chemotherapy resistance remains unknown. Here, we evaluated the impact of the MEK5/ERK5 cascade in colon cancer cell sensitivity to 5-fluorouracil (5-FU). Increased ERK5 expression was correlated with poor overall survival in colon cancer patients. In colon cancer cells, 5-FU exposure impaired endogenous KRAS/MEK5/ERK5 expression and/or activation. In turn, MEK5 constitutive activation reduced 5-FU-induced cytotoxicity. Using genetic and pharmacological approaches, we showed that ERK5 inhibition increased caspase-3/7 activity and apoptosis following 5-FU exposure. Mechanistically, this was further associated with increased p53 transcriptional activation of p21 and PUMA. In addition, ERK5 inhibition increased the response of HCT116 p53+/+ cells to 5-FU, but failed to sensitize HCT116 p53-/- cells to the cytotoxic effects of this chemotherapeutic agent, suggesting a p53-dependent axis mediating 5-FU sensitization. Finally, ERK5 inhibition using XMD8-92 was shown to increase the antitumor effects of 5-FU in a murine subcutaneous xenograft model, enhancing apoptosis while markedly reducing tumor growth. Collectively, our results suggest that ERK5-targeted inhibition provides a promising therapeutic approach to overcome resistance to 5-FU-based chemotherapy and improve colon cancer treatment.
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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.