Progression of prostate cancer (PCa) is characterized by metastasis and castration resistance after response to androgen deprivation. Therapeutic options are limited, causing high morbidity and lethality. Recently, we reported pro-oncogenic implications of the Mediator subunits cyclin-dependent kinase (CDK) 8 and 19 for the progression of PCa. In this study, the aim was to explore underlying molecular mechanisms and to test effects of novel CDK8/CDK19 inhibitors. PC3, DU145, LNCaP, and androgen-independent LNCaP Abl were used for in vitro experiments. Two inhibitors and CDK19 overexpression were used to modify CDK8/CDK19 activity. Thiazolyl blue tetrazolium bromide (MTT) assay, propidium iodide staining, wound healing assay, Boyden chambers, and adhesion assays in various experimental conditions were used to investigate cell viability, cell cycle, migration, and adhesion, respectively. Peptide-kinase screen using the PamGene platform was conducted to identify phosphorylated targets. Combining CDK8/CDK19 inhibitors with anti-androgens lead to synergistic antiproliferative effects and sensitized androgen-independent cells to bicalutamide. CDK8/CDK19 inhibition resulted in reduced migration and increased collagen I-dependent adhesion. Phosphorylation of multiple peptides linked to cancer progression was identified to be dependent on CDK8/CDK19. In summary, this study substantially supports recent findings on CDK8/CDK19 in PCa progression. These findings contribute to a better understanding of underlying pro-oncogenic effects, which is needed to develop CDK8/CDK19 as a therapeutic target in PCa.

Original languageEnglish
JournalAmerican Journal of Pathology
Issue number5
Pages (from-to)813-823
Number of pages11
Publication statusPublished - 05.2022

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)
  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)


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