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    GENE:

    MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)

    i
    Other names: MAP3K8, Mitogen-Activated Protein Kinase Kinase Kinase 8, , Tumor Progression Locus 2, Proto-Oncogene C-Cot, MEKK8, Tpl-2 , C-COT, ESTF, COT, EST, Proto-Oncogene Serine/Threoine Protein Kinase, Augmented In Rheumatoid Arthritis 2, Cot (Cancer Osaka Thyroid) Oncogene, Serine/Threonine-Protein Kinase Cot, Cancer Osaka Thyroid Oncogene, Ewing Sarcoma Transformant, MAP3K8, AURA2, TPL-2, TPL2
    20d
    The ASFV CD2v protein inhibits apoptosis by inducing proteasomal degradation of BimEL via activation of the TPL2-MEK-ERK signaling pathway. (PubMed, J Virol)
    This dual action helps create a protective, pro-survival cellular environment that facilitates viral spread and persistence. Understanding this novel apoptotic suppression mechanism advances our knowledge of ASFV-host interactions and highlights potential new avenues for therapeutic intervention.
    Journal
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    MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
    3ms
    Identification and validation of a diagnostic and prognostic model based on immune escape and cancer-associated fibroblast-related genes in lung adenocarcinoma. (PubMed, Medicine (Baltimore))
    Kyoto Encyclopedia of Genes and Genomes analysis revealed pathways related to morphine addiction and protein digestion/absorption...Sensitivity to chemotherapeutics, such as AZD6482, ABT-263, A-770041, and BMS-536924, was observed in LUAD. Reverse transcription-quantitative polymerase chain reaction validation results demonstrated that KRT8 and S100A16 were significantly upregulated in tumor tissues, while COL4A3 and SMAD9 expression was downregulated, which was consistent with the TCGA-LUAD database analysis. In conclusion, 6 genes (KRT8, S100A16, COL4A3, SMAD9, MAP3K8, and CCDC146) were identified as potential biomarkers, offering valuable insights into LUAD pathogenesis and therapeutic strategies.
    Journal
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    CD8 (cluster of differentiation 8) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) • S100A16 (S100 Calcium Binding Protein A16) • SMAD9 (SMAD Family Member 9)
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    navitoclax (ABT 263) • AZD6482 • BMS-536924
    3ms
    Chromatin remodeling enhances MAP3K8 expression in HAM: a key pathogenesis for therapeutic intervention. (PubMed, Nat Commun)
    Crucially, we demonstrate that mitogen-activated protein kinase kinase (MEK) inhibitors effectively suppress the MAP3K8-MEK signaling cascade and significantly mitigated inflammatory pathogenesis in an ex vivo culture assay. Our findings provide critical insights into the virus-host interactions underpinning HAM and propose the MAP3K8-MEK-ERK axis as a promising therapeutic target for this challenging condition.
    Journal
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    MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) • FOSL2 (FOS Like 2) • JUN (Jun proto-oncogene)
    4ms
    Increased EGFR/HER2 Pathway Activation Contributes to Skin Tumorigenesis in Tpl2-/- Mice. (PubMed, Cancers (Basel))
    Treatment with Gefitinib or Lapatinib reduced papilloma numbers by 88% and 50%, respectively, while restoring cSCC numbers to Tpl2+/+ levels. These findings indicate that ErbB targeting represents a promising therapeutic strategy for cSCCs arising from MAPK pathway dysregulation.
    Preclinical • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
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    HER-2 expression
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    gefitinib • lapatinib
    4ms
    TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ. (PubMed, Int J Biol Sci)
    Silencing TPL2 via siRNA or pharmacological inhibition suppressed GC cell proliferation and enhanced sensitivity to doxorubicin (Adriamycin), whereas TPL2 overexpression promoted tumor growth and chemoresistance...This study identifies a novel TPL2/PPARδ positive feedback regulatory loop that drives GC progression and chemoresistance. Targeting this axis may provide new therapeutic strategies not only for GC but also for other diseases associated with pathological hypoxia.
    Journal
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    MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
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    doxorubicin hydrochloride
    6ms
    A four-gene signature identified by integrated transcriptomic analysis for differential diagnosis and prognosis of uterine smooth muscle tumors. (PubMed, Front Oncol)
    Our study identifies ABLIM1, FHL5, MAP3K8, and TOP2A as key molecular drivers of uterine smooth muscle tumorigenesis. The four-gene signature shows promise as a biomarker panel for early diagnosis and differentiation between tumor and normal tissues, providing a potential molecular foundation for targeted therapeutic strategies.
    Journal • Gene Signature
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    TOP2A (DNA topoisomerase 2-alpha) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
    8ms
    Analysis of the Expression Patterns of Tumor Necrosis Factor Alpha Signaling Pathways and Regulatory MicroRNAs in Astrocytic Tumors. (PubMed, Int J Mol Sci)
    Our findings establish a multi-layered regulatory mechanism of TNF-α signaling in astrocytic tumors. These data highlight the TNF-α/IL-1β/MAP3K8 axis as a critical driver of glioma aggressiveness and a potential therapeutic target.
    Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • MIR34A (MicroRNA 34a-5p) • IL1B (Interleukin 1, beta) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) • MAP2K7 (Mitogen-Activated Protein Kinase Kinase 7) • MIR30E (MicroRNA 30e)
    11ms
    TPL2 kinase activity is required for Il1b transcription during LPS priming but dispensable for NLRP3 inflammasome activation. (PubMed, Front Immunol)
    Our results demonstrate that TPL2 kinase activity is differentially required for the expression of inflammasome precursor cytokines and components but is dispensable for inflammasome activation. These data provide the foundation for the further exploration of TPL2 kinase inhibitor as a potential therapeutic in inflammatory diseases.
    Journal
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    IL18 (Interleukin 18) • IL1B (Interleukin 1, beta) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) • NLRP3 (NLR Family Pyrin Domain Containing 3)
    12ms
    Identifcation of the FGF family as therapeutic targets and prognostic biomarkers in the microenvironment of head and neck squamous cell carcinoma. (PubMed, SLAS Technol)
    Our data may shed new light on the choice of immunotherapeutic targets and predictive biomarkers in HNSC.
    Journal • IO biomarker
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    EGFR (Epidermal growth factor receptor) • FGF19 (Fibroblast growth factor 19) • CD4 (CD4 Molecule) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • SYK (Spleen tyrosine kinase) • AURKB (Aurora Kinase B) • FGF (Fibroblast Growth Factor) • FGF21 (Fibroblast Growth Factor 21) • ATF4 (Activating Transcription Factor 4) • FGF23 (Fibroblast Growth Factor 23) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) • BUB1 (BUB1 Mitotic Checkpoint Serine/Threonine Kinase) • CAMK2A (Calcium/Calmodulin Dependent Protein Kinase II Alpha) • FGF7 (Fibroblast Growth Factor 7) • FGF8 (Fibroblast Growth Factor 8) • MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3) • MAPK3 (Mitogen-Activated Protein Kinase 3) • RELA (RELA Proto-Oncogene)
    12ms
    CD28 is superior to 4-1BB costimulation in generating CAR-NK cells for tumor immunotherapy. (PubMed, Exp Hematol Oncol)
    Silencing or inhibiting MAP3K8 impaired the anti-tumor activity of 28z CAR-NK cells, while its overexpression substantially improved the function of BBz CAR-NK cells. These findings provide new insights into how CD28 costimulation boosts CAR-NK cell efficacy, supporting its use into NK cell-specific CARs for cancer immunotherapy, and highlight MAP3K8 as a potential target for optimizing BBz CAR-NK cell therapy.
    Journal • IO biomarker
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    MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
    1year
    SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma. (PubMed, Front Immunol)
    Furthermore, its overexpression promoted macrophage polarization towards the M2-like phenotype and promoted the migration of M2-like macrophage cells and C-C Motif Chemokine Ligand 5 (CCL5) was the key mediator in the pro-cancer effect of SECTM1. In a Conclusion, our study established a prognostic prediction model based on immune-related gene signature, which provided a reliable prognostic tool for ESCC and identified SECTM1 as a potential biomarker in ESCC.
    Journal
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    MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) • SECTM1 (Secreted and transmembrane 1)