ArticleCancer research2018
CDK8 Selectively Promotes the Growth of Colon Cancer Metastases in the Liver by Regulating Gene Expression of TIMP3 and Matrix Metalloproteinases.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
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- Interpretable and scalable spatial gene set activity analysis with GESSO uncovers functional tissue architecture.bioRxiv : the preprint server for biology · 2026Article
- Low expression of OXCT1 promote colorectal cancer liver metastasis by upregulating CDK8 and β-catenin via H3 acetylation.Genes & diseases · 2026Article
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- Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death.Cell death & disease · 2025Article
- Transcriptional regulation of protein synthesis by mediator kinase represents a therapeutic vulnerability in MYC-driven medulloblastoma.Nature communications · 2025Article
- Cancer-associated fibroblast-derived extracellular vesicles facilitate metastasis in hepatocellular carcinoma by delivering CTGF.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Targeting Transcriptional Cyclin-Dependent Kinases in Cancer.Molecular cancer therapeutics · 2025Review
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- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Mediator kinase inhibitors suppress triple-negative breast cancer growth and extend tumor suppression by mTOR and AKT inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma.World journal of hepatology · 2024Article
- Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1Molecular cancer · 2024Article
- Mediator kinase module proteins, genetic alterations and expression of super-enhancer regulated genes in colorectal cancer.Pharmacological reports : PR · 2024Article
- Mediator kinase inhibition reverses castration resistance of advanced prostate cancer.The Journal of clinical investigation · 2024Article
- Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.International journal of molecular sciences · 2024Review
- Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension.Kidney & blood pressure research · 2024Article
- Unveiling the immune symphony: decoding colorectal cancer metastasis through immune interactions.Frontiers in immunology · 2024Review
- Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2024Review
- GDF15 deficiency hinders human trophoblast invasion to mediate pregnancy loss through downregulating Smad1/5 phosphorylation.iScience · 2023Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
: Unresectable hepatic metastases of colon cancer respond poorly to existing therapies and are a major cause of colon cancer lethality. In this study, we evaluated the therapeutic viability of targeting the mediator kinase CDK8, an early clinical stage drug target, as a means to suppress metastasis of colon cancer. CDK8 was amplified or overexpressed in many colon cancers and CDK8 expression correlated with shorter patient survival. Knockdown or inhibition of CDK8 had little effect on colon cancer cell growth but suppressed metastatic growth of mouse and human colon cancer cells in the liver. This effect was due in part to inhibition of already established hepatic metastases, indicating therapeutic potential of CDK8 inhibitors in the metastatic setting. In contrast, knockdown or inhibition of CDK8 had no significant effect on the growth of tumors implanted subcutaneously, intrasplenically, or orthotopically in the cecum. CDK8 mediated colon cancer growth in the liver through downregulation of matrix metalloproteinase (MMP) inhibitor TIMP3 via TGFβ/SMAD-driven expression of a TIMP3-targeting microRNA, miR-181b, along with induction of Mmp3 in murine or MMP9 in human colon cancer cells via Wnt/β-catenin-driven transcription. These findings reveal a new mechanism for negative regulation of gene expression by CDK8 and a site-specific role for CDK8 in colon cancer hepatic metastasis. Our results indicate the utility of CDK8 inhibitors for the treatment of colon cancer metastases in the liver and suggest that CDK8 inhibitors may be considered in other therapeutic settings involving TGFβ/SMAD or Wnt/β-catenin pathway activation. SIGNIFICANCE: These findings demonstrate that inhibition of the transcription-regulating kinase CDK8 exerts a site-specific tumor-suppressive effect on colon cancer growth in the liver, representing a unique therapeutic opportunity for the treatment of advanced colon cancer.
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