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

Prakash, Varsha; Carson, Brittany B.; Feenstra, Jennifer M.; Dass, Randall A.; Sekyrova, Petra; Hoshino, Ayuko; Petersen, Julian; Guo, Yuan; Parks, Matthew M. and Kurylo, Chad M., et al. (2019) In Nature Communications 10(1).
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... (More)

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.

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@article{e380261f-3aae-4b18-b2a0-b07bb5b5c67f,
  abstract     = {<p>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.</p>},
  articleno    = {2110},
  author       = {Prakash, Varsha and Carson, Brittany B. and Feenstra, Jennifer M. and Dass, Randall A. and Sekyrova, Petra and Hoshino, Ayuko and Petersen, Julian and Guo, Yuan and Parks, Matthew M. and Kurylo, Chad M. and Batchelder, Jake E. and Haller, Kristian and Hashimoto, Ayako and Rundqivst, Helene and Condeelis, John S. and Allis, C. David and Drygin, Denis and Nieto, M. Angela and Andäng, Michael and Percipalle, Piergiorgio and Bergh, Jonas and Adameyko, Igor and Farrants, Ann Kristin Östlund and Hartman, Johan and Lyden, David and Pietras, Kristian and Blanchard, Scott C. and Vincent, C. Theresa},
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease},
  url          = {http://dx.doi.org/10.1038/s41467-019-10100-8},
  volume       = {10},
  year         = {2019},
}