A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours

Madhuri Kalathur, Alberto Toso, Jingjing Chen, Ajinkya Revandkar, Claudia Danzer-Baltzer, Ilaria Guccini, Abdullah Alajati, Manuela Sarti, Sandra Pinton, Lara Brambilla, Diletta Di Mitri, Giuseppina Carbone, R. Garcia-Escudero, Alessandro Padova, Letizia Magnoni, Alessia Tarditi, Laura Maccari, Federico Malusa, Ravi Kiran Reddy Kalathur, Lorenzo A. PinnaGiorgio Cozza, Maria Ruzzene, Nicolas Delaleu, Carlo V. Catapano, Ian J. Frew, Andrea Alimonti

Research output: Contribution to journalArticle

Abstract

Enhancement of cellular senescence in tumours triggers a stable cell growth arrest and activation of an antitumour immune response that can be exploited for cancer therapy. Currently, there are only a limited number of targeted therapies that act by increasing senescence in cancers, but the majority of them are not selective and also target healthy cells. Here we developed a chemogenomic screening to identify compounds that enhance senescence in PTEN-deficient cells without affecting normal cells. By using this approach, we identified casein kinase 2 (CK2) as a pro-senescent target. Mechanistically, we show that Pten loss increases CK2 levels by activating STAT3. CK2 upregulation in Pten null tumours affects the stability of Pml, an essential regulator of senescence. However, CK2 inhibition stabilizes Pml levels enhancing senescence in Pten null tumours. Taken together, our screening strategy has identified a novel STAT3-CK2-PML network that can be targeted for pro-senescence therapy for cancer.

Original languageEnglish
Article number7227
JournalNature Communications
Volume6
DOIs
Publication statusPublished - Jun 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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  • Cite this

    Kalathur, M., Toso, A., Chen, J., Revandkar, A., Danzer-Baltzer, C., Guccini, I., Alajati, A., Sarti, M., Pinton, S., Brambilla, L., Di Mitri, D., Carbone, G., Garcia-Escudero, R., Padova, A., Magnoni, L., Tarditi, A., Maccari, L., Malusa, F., Kalathur, R. K. R., ... Alimonti, A. (2015). A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours. Nature Communications, 6, [7227]. https://doi.org/10.1038/ncomms8227