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Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in

Johannes Brägelmann1,2,3,4, Niklas Klümper5, Anne Offermann5

  • 1Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 29, 2016
PubMed

Insights

The Mediator complex shows distinct subunit compositions across cancers. CDK19 and CDK8 are overexpressed in advanced prostate cancer, suggesting they are potential therapeutic targets for this disease.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • The Mediator complex regulates gene expression and is implicated in cancer.
  • Understanding Mediator complex alterations in cancer can lead to new therapies.

Purpose of the Study:

  • To systematically analyze Mediator complex subunit expression across various cancer types.
  • To investigate the specific role of CDK19 and CDK8 in prostate cancer progression and metastasis.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) data for expression profiling across 23 cancer types.
  • Validated prostate cancer findings using independent cohorts and immunohistochemistry.
  • Employed siRNA knockdown and inhibitor treatments in cell lines to assess CDK19/CDK8 function.

Main Results:

  • Mediator complex composition varies significantly between tumor types.
  • Prostate cancer uniquely exhibits high CDK19 expression, correlated with aggressiveness.
  • CDK19 and CDK8 levels increase during prostate cancer progression, particularly in metastases.
  • Inhibition of CDK19/CDK8 reduced cancer cell migration and invasion in vitro.

Conclusions:

  • Distinct Mediator complex expression profiles suggest differential transcriptional regulation in cancers.
  • CDK19 and CDK8 are specifically upregulated in advanced prostate cancer.
  • CDK19 and CDK8 represent promising therapeutic targets for advanced prostate cancer.

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