ArticleCancer research2016
Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 47 citations in OpenAlex.
- MLK4 orchestrates macrophage-induced triple-negative breast cancer invasion and ECM remodeling via enhanced paracrine signaling and NF-κB-MMP axis activation.Cell death & disease · 2026Article
- Chemical Composition, Antioxidant, Enzyme Inhibition and Anticancer Activities: Effects on the Expression of Genes Related to Apoptosis and the Polyamine Pathway and Molecular Docking Analyses ofCurrent issues in molecular biology · 2025Article
- Wnt signalosome assembly is governed by conformational flexibility of Axin and by the AP2 clathrin adaptor.Nature communications · 2025Article
- Molecular Dynamics Simulation of Kir6.2 Variants Reveals Potential Association with Diabetes Mellitus.Molecules (Basel, Switzerland) · 2024Article
- The Expression Profiles and Clinical Significance of Mixed Lineage Kinases in Glioma.Mediators of inflammation · 2024Article
- MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5.Oncogenesis · 2023Article
- Article
- Chemical Composition and the Anticancer, Antimicrobial, and Antioxidant Properties ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance.Cell death & disease · 2021Article
- Population pharmacokinetics of ATR inhibitor berzosertib in phase I studies for different cancer types.Cancer chemotherapy and pharmacology · 2021Article
- Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2021Article
- Article
- Orange is the new black: Kinases are the new master regulators of tumor suppression.IUBMB life · 2019Review
- Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells.Oncogene · 2019Article
- Mixed lineage kinase-4 promotes gastric carcinoma tumorigenesis through suppression of the c-Jun N-terminal kinase signaling pathway.Experimental and therapeutic medicine · 2018Article
- Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors.PloS one · 2018Article
- Osmotic and heat stress-dependent regulation of MLK4β and MLK3 by the CHIP E3 ligase in ovarian cancer cells.Cellular signalling · 2017Article
- Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/ MMP9 signaling.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
MLK4 is a member of the mixed-lineage family of kinases that regulate the JNK, p38, and ERK kinase signaling pathways. MLK4 mutations have been identified in various human cancers, including frequently in colorectal cancer, where their function and pathobiological importance have been uncertain. In this study, we assessed the functional consequences of MLK4 mutations in colon tumorigenesis. Biochemical data indicated that a majority of MLK4 mutations are loss-of-function (LOF) mutations that can exert dominant-negative effects. In seeking to understand the abrogated activity of these mutants, we elucidated a new MLK4 catalytic domain structure. To determine whether MLK4 is required to maintain tumorigenic phenotypes, we reconstituted its signaling axis in colon cancer cells harboring MLK4-inactivating mutations. We found that restoring MLK4 activity reduced cell viability, proliferation, and colony formation in vitro and delayed tumor growth in vivo. Mechanistic investigations established that restoring the function of MLK4 selectively induced the JNK pathway and its downstream targets, cJUN, ATF3, and the cyclin-dependent kinase inhibitors CDKN1A and CDKN2B. Our work indicates that MLK4 is a novel tumor-suppressing kinase harboring frequent LOF mutations that lead to diminished signaling in the JNK pathway and enhanced proliferation in colon cancer.
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.