Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease

Varsha Prakash, Brittany B. Carson, Jennifer M. Feenstra, Randall A. Dass, Petra Sekyrova, Ayuko Hoshino, Julian Petersen, Yuan Guo, Matthew M. Parks, Chad M. Kurylo, Jake E. Batchelder, Kristian Haller, Ayako Hashimoto, Helene Rundqivst, John S. Condeelis, C. David Allis, Denis Drygin, M. Angela Nieto, Michael Andäng, Piergiorgio PercipalleJonas Bergh, Igor Adameyko, Ann Kristin Östlund Farrants, Johan Hartman, David Lyden, Kristian Pietras, Scott C. Blanchard, C. Theresa Vincent

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution of Epithelial-to-Mesenchymal Transition (EMT), a migratory cellular program associated with development and tumor metastasis, is fueled by upregulation of ribosome biogenesis during G1/S arrest. This unexpected EMT feature is independent of species and initiating signal, and is accompanied by release of the repressive nucleolar chromatin remodeling complex (NoRC) from rDNA, together with recruitment of the EMT-driving transcription factor Snai1 (Snail1), RNA Polymerase I (Pol I) and the Upstream Binding Factor (UBF). EMT-associated ribosome biogenesis is also coincident with increased nucleolar recruitment of Rictor, an essential component of the EMT-promoting mammalian target of rapamycin complex 2 (mTORC2). Inhibition of rRNA synthesis in vivo differentiates primary tumors to a benign, Estrogen Receptor-alpha (ERα) positive, Rictor-negative phenotype and reduces metastasis. These findings implicate the EMT-associated ribosome biogenesis program with cellular plasticity, de-differentiation, cancer progression and metastatic disease.

Original languageEnglish (US)
Article number2110
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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

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    Prakash, V., Carson, B. B., Feenstra, J. M., Dass, R. A., Sekyrova, P., Hoshino, A., Petersen, J., Guo, Y., Parks, M. M., Kurylo, C. M., Batchelder, J. E., Haller, K., Hashimoto, A., Rundqivst, H., Condeelis, J. S., Allis, C. D., Drygin, D., Nieto, M. A., Andäng, M., ... Vincent, C. T. (2019). Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease. Nature communications, 10(1), [2110]. https://doi.org/10.1038/s41467-019-10100-8