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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

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

Author

  • 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 Percipalle
  • Jonas Bergh
  • Igor Adameyko
  • Ann Kristin Östlund Farrants
  • Johan Hartman
  • David Lyden
  • Kristian Pietras
  • Scott C. Blanchard
  • C. Theresa Vincent
Show all

Summary, in English

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.

Department/s

  • Experimental oncology
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2019

Language

English

Publication/Series

Nature Communications

Volume

10

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology
  • Cancer and Oncology

Status

Published

Research group

  • Experimental oncology

ISBN/ISSN/Other

  • ISSN: 2041-1723