ArticlePloS one2014
Mitogen-activated protein kinase kinase 4 (MAP2K4) promotes human prostate cancer metastasis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- Integrative Proteomic Analysis Implicates Inhibition of Intracellular Protein Trafficking in Therapy-Induced Migrastasis in Prostate Cancer.Proteomes · 2026Article
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- Effect of miR-6767-5p on breast cancer cell phenotype and its regulatory mechanism.Scientific reports · 2025Article
- Research and progress of microRNA-136 in metastatic tumors.Frontiers in oncology · 2025Review
- miR-4486 inhibits colorectal cancer proliferation via targeting MAP2K4 to inhibit the activation of the p38MAPK/JNK signaling.Heliyon · 2024Article
- Molecular profiling and prognostic analysis in Chinese cholangiocarcinoma: an observational, retrospective single-center study.Investigational new drugs · 2024Observational
- Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor.Gynecologic oncology · 2023Article
- MKK4 Inhibitors-Recent Development Status and Therapeutic Potential.International journal of molecular sciences · 2023Review
- Review
- Mobile element insertions and associated structural variants in longitudinal breast cancer samples.Scientific reports · 2021Article
- Integrated mutational landscape analysis of uterine leiomyosarcomas.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genomic Landscape of Uterine Sarcomas Defined Through Prospective Clinical Sequencing.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Observational
- Huai Qi Huang-induced Apoptosis via Down-regulating PRKCH and Inhibiting RAF/MEK/ERK Pathway in PhCurrent medical science · 2020Article
- MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis.Veterinary research · 2020Article
- The autoinhibited state of MKK4: Phosphorylation, putative dimerization and R134W mutant studied by molecular dynamics simulations.Computational and structural biotechnology journal · 2020Article
- MAP2K4 interacts with Vimentin to activate the PI3K/AKT pathway and promotes breast cancer pathogenesis.Aging · 2019Article
- Modeling MEK4 Kinase Inhibitors through Perturbed Electrostatic Potential Charges.Journal of chemical information and modeling · 2019Article
- Synthesis and Biological Evaluation of 3-Arylindazoles as Selective MEK4 Inhibitors.ChemMedChem · 2019Article
- Intronic miR-744 Inhibits Glioblastoma Migration by Functionally Antagonizing Its Host Gene MAP2K4.Cancers · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Prostate cancer (PCa) is the second leading cause of cancer death in the US. Death from PCa primarily results from metastasis. Mitogen-activated protein kinase kinase 4 (MAP2K4) is overexpressed in invasive PCa lesions in humans, and can be inhibited by small molecule therapeutics that demonstrate favorable activity in phase II studies. However, MAP2K4's role in regulating metastatic behavior is controversial and unknown. To investigate, we engineered human PCa cell lines which overexpress either wild type or constitutive active MAP2K4. Orthotopic implantation into mice demonstrated MAP2K4 increases formation of distant metastasis. Constitutive active MAP2K4, though not wild type, increases tumor size and circulating tumor cells in the blood and bone marrow. Complementary in vitro studies establish stable MAP2K4 overexpression promotes cell invasion, but does not affect cell growth or migration. MAP2K4 overexpression increases the expression of heat shock protein 27 (HSP27) protein and protease production, with the largest effect upon matrix metalloproteinase 2 (MMP-2), both in vitro and in mouse tumor samples. Further, MAP2K4-mediated increases in cell invasion are dependent upon heat shock protein 27 (HSP27) and MMP-2, but not upon MAP2K4's immediate downstream targets, p38 MAPK or JNK. We demonstrate that MAP2K4 increases human PCa metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. These findings provide a mechanistic explanation for human studies linking increases in HSP27 and MMP-2 to progression to metastatic disease. MAP2K4 is validated as an important therapeutic target for inhibiting human PCa metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.