ArticleOncotarget2017
Downregulation of phosphorylated MKK4 is associated with a poor prognosis in colorectal cancer patients.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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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
8 citing papers in PubMed, 10 citations in OpenAlex.
- Expression and Clinical Significance ofInternational journal of molecular sciences · 2025Article
- Review
- Metastasis suppressor genes in clinical practice: are they druggable?Cancer metastasis reviews · 2023Review
- Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.Nature communications · 2020Article
- MAP Kinases Pathways in Gastric Cancer.International journal of molecular sciences · 2020Review
- The autoinhibited state of MKK4: Phosphorylation, putative dimerization and R134W mutant studied by molecular dynamics simulations.Computational and structural biotechnology journal · 2020Article
- Saikosaponin D Inhibits Proliferation and Promotes Apoptosis Through Activation of MKK4-JNK Signaling Pathway in Pancreatic Cancer Cells.OncoTargets and therapy · 2020Article
- CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N-terminal kinase signaling and influences malignant metastasis. Here, we used immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine their association with the clinicopathological features of a pilot set of patient samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation set of CRC cases with accompanying follow-up data to confirm their clinicopathological and prognostic significance. pMKK4 levels, which were high in 79.17% of NCM samples, were downregulated in 33.33% of CA and 63.54% of CRC samples. pMKK4 downregulation was associated with metastasis, especially to the liver. In the validation set, pMKK4 downregulation was associated with increases in invasive depth, lymph node metastasis, distant metastasis, and TNM stage. Univariate analysis indicated that pMKK4 score, tumor differentiation, and TNM stage were correlated with disease-free survival and overall survival. Multivariate analysis indicated that decreased pMKK4 expression was an independent risk factor for disease-free survival in CRC patients. These results suggest that CRC patients with low pMKK4 immunochemistry scores should be monitored carefully for early detection of possible recurrences, especially liver metastasis.
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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.