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 Percipalle, Jonas Bergh, Igor Adameyko, Ann-Kristin Östlund Farrants, Johan Hartman, David Lyden, Kristian Pietras, Scott C. Blanchard () and C. Theresa Vincent ()
Additional contact information
Varsha Prakash: Karolinska Institutet
Brittany B. Carson: Karolinska Institutet
Jennifer M. Feenstra: Karolinska Institutet
Randall A. Dass: Weill Cornell Medicine
Petra Sekyrova: Uppsala University
Ayuko Hoshino: Weill Cornell Medicine
Julian Petersen: Karolinska Institutet
Yuan Guo: The Wenner-Gren Institute, Stockholm University
Matthew M. Parks: Weill Cornell Medicine
Chad M. Kurylo: Weill Cornell Medicine
Jake E. Batchelder: Weill Cornell Medicine
Kristian Haller: Center for Molecular Pathology, Lund University
Ayako Hashimoto: Weill Cornell Medicine
Helene Rundqivst: Karolinska Institute
John S. Condeelis: Albert Einstein College of Medicine
C. David Allis: The Rockefeller University
Denis Drygin: Pimera, Inc
M. Angela Nieto: Instituto de Neurociencias, CSIC-UMH
Michael Andäng: Uppsala University
Piergiorgio Percipalle: New York University Abu Dhabi
Jonas Bergh: Karolinska Institutet and University Hospital
Igor Adameyko: Karolinska Institutet
Ann-Kristin Östlund Farrants: The Wenner-Gren Institute, Stockholm University
Johan Hartman: Karolinska Institutet and University Hospital
David Lyden: Weill Cornell Medicine
Kristian Pietras: Center for Molecular Pathology, Lund University
Scott C. Blanchard: Weill Cornell Medicine
C. Theresa Vincent: Karolinska Institutet

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10100-8

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DOI: 10.1038/s41467-019-10100-8

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