Ribosomal protein S11 influences glioma response to TOP2 poisons

Chidiebere U. Awah, Li Chen, Mukesh Bansal, Aayushi Mahajan, Jan Winter, Meeki Lad, Louisa Warnke, Edgar Gonzalez-Buendia, Cheol Park, Daniel Zhang, Eric Feldstein, Dou Yu, Markella Zannikou, Irina V. Balyasnikova, Regina Martuscello, Silvana Konerman, Balázs Győrffy, Kirsten B. Burdett, Denise M. Scholtens, Roger StuppAtique Uddin Ahmed, Patrick Hsu, Adam M. Sonabend*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Topoisomerase II poisons are one of the most common class of chemotherapeutics used in cancer. We and others had shown that a subset of glioblastomas, the most malignant of all primary brain tumors in adults, is responsive to TOP2 poisons. To identify genes that confer susceptibility to this drug in gliomas, we performed a genome-scale CRISPR knockout screen with etoposide. Genes involved in protein synthesis and DNA damage were implicated in etoposide susceptibility. To define potential biomarkers for TOP2 poisons, CRISPR hits were overlapped with genes whose expression correlates with susceptibility to this drug across glioma cell lines, revealing ribosomal protein subunit RPS11, 16, and 18 as putative biomarkers for response to TOP2 poisons. Loss of RPS11 led to resistance to etoposide and doxorubicin and impaired the induction of proapoptotic gene APAF1 following treatment. The expression of these ribosomal subunits was also associated with susceptibility to TOP2 poisons across cell lines from gliomas and multiple other cancers.

Original languageEnglish (US)
Pages (from-to)5068-5081
Number of pages14
JournalOncogene
Volume39
Issue number27
DOIs
StatePublished - Jul 2 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Awah, C. U., Chen, L., Bansal, M., Mahajan, A., Winter, J., Lad, M., Warnke, L., Gonzalez-Buendia, E., Park, C., Zhang, D., Feldstein, E., Yu, D., Zannikou, M., Balyasnikova, I. V., Martuscello, R., Konerman, S., Győrffy, B., Burdett, K. B., Scholtens, D. M., ... Sonabend, A. M. (2020). Ribosomal protein S11 influences glioma response to TOP2 poisons. Oncogene, 39(27), 5068-5081. https://doi.org/10.1038/s41388-020-1342-0