ArticleCellular and molecular life sciences : CMLS2022
The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Current status and targeted therapies in endometrial cancer: Molecular classification-driven treatment strategies (Review).Oncology letters · 2026Review
- Dual mechanism of human ATG10S in suppressing MEF2A-Driven pro-inflammatory responses.Autophagy · 2026Article
- Comprehensive Bioinformatic and miRNA-Driven Analysis of the Multimeric Canonical I Kappa B Kinase (IKK) Complex in Uterine Corpus Endometrial Carcinoma (UCEC).Biomolecules · 2026Article
- A different MAPK, ERK5 plays a critical role in cell specification and differentiation.Biochemistry and biophysics reports · 2026Review
- MAPK ERK5 is a novel regulator of MHC-I in cancer cells.Cell communication and signaling : CCS · 2026Article
- VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma.International journal of biological sciences · 2026Article
- Platelet-activating factor induces ferroptosis by binding to ATF3 and inhibiting the SLC7A11/GPX4 axis to suppress the progression of endometrial carcinoma.Biology direct · 2025Article
- The Emerging Role of FAM171A2 in Gynecological Malignancies: Bioinformatic Insights from UCEC and Ovarian Cancer.International journal of molecular sciences · 2025Article
- The Discovery of Small ERK5 Inhibitors via Structure-Based Virtual Screening, Biological Evaluation and MD Simulations.Molecules (Basel, Switzerland) · 2025Article
- DNA hypomethylated modified lncRNA MALAT1 promotes atherosclerotic cardiovascular disease progression through NF-κB signaling pathway regulating cholesterol metabolism and inflammatory response.Biochemistry and biophysics reports · 2025Article
- Molecular mechanism of tumor-infiltrating immune cells regulating endometrial carcinoma.Genes & diseases · 2025Review
- Comprehensive analysis of immunogenic cell death-related genes in liver ischemia-reperfusion injury.Frontiers in immunology · 2025Article
- Is the MAPK ERK5 the nexus from FAO to NK cell-mediated metastasis immune surveillance?Frontiers in immunology · 2025Review
- IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway.Cancer gene therapy · 2024Article
- IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling.Journal of virology · 2024Article
- Targeting NF-κB in Hepatic Ischemia-Reperfusion Alleviation: from Signaling Networks to Therapeutic Targeting.Molecular neurobiology · 2024Review
- Article
- Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond.Frontiers in genetics · 2024Review
- MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.Cell death & disease · 2023Article
- Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Endometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed alterations in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell proliferation and survival. We propose the ERK5/NF-κB axis as new target for EC 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.