Autre Publication Scientifique Année : 2019

CDK8 and CDK19 kinases have non-redundant oncogenic functions in hepatocellular carcinoma

Geronimo Dubra
Anthony Lozano
Jacqueline Butterworth
  • Fonction : Auteur
Jessica Zucman-Rossi
Urszula Hibner
Daniel Fisher
  • Fonction : Auteur
Damien Gregoire

Résumé

Hepatocellular carcinoma (HCC) is a common cancer with high mortality. The limited therapeutic options for advanced disease include treatment with Sorafenib, a multi-kinase inhibitor whose targets include the Mediator kinase CDK8. Since CDK8 has reported oncogenic activity in Wnt-dependent colorectal cancer, we investigated whether it is also involved in HCC. We find that CDK8 and its paralogue CDK19 are significantly overexpressed in HCC patients, where high levels correlate with poor prognosis. Liver-specific genetic deletion of CDK8 in mice is well supported and protects against chemical carcinogenesis. Deletion of either CDK8 or CDK19 in hepatic precursors had little effect on gene expression in exponential cell growth but prevented oncogene-induced transformation. This phenotype was reversed by concomitant deletion of TP53. These data support important and non-redundant roles for mediator kinases in liver carcinogenesis, where they genetically interact with the TP53 tumor suppressor.

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Dates et versions

hal-02373077 , version 1 (20-11-2019)

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Katarina Bacevic, Susana Prieto, Stefano Caruso, Alain Camasses, Geronimo Dubra, et al.. CDK8 and CDK19 kinases have non-redundant oncogenic functions in hepatocellular carcinoma. 2019, ⟨10.1101/789586⟩. ⟨hal-02373077⟩
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