TY - JOUR
T1 - Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease
AU - Prakash, Varsha
AU - Carson, Brittany B.
AU - Feenstra, Jennifer M.
AU - Dass, Randall A.
AU - Sekyrova, Petra
AU - Hoshino, Ayuko
AU - Petersen, Julian
AU - Guo, Yuan
AU - Parks, Matthew M.
AU - Kurylo, Chad M.
AU - Batchelder, Jake E.
AU - Haller, Kristian
AU - Hashimoto, Ayako
AU - Rundqivst, Helene
AU - Condeelis, John S.
AU - Allis, C. David
AU - Drygin, Denis
AU - Nieto, M. Angela
AU - Andäng, Michael
AU - Percipalle, Piergiorgio
AU - Bergh, Jonas
AU - Adameyko, Igor
AU - Farrants, Ann Kristin Östlund
AU - Hartman, Johan
AU - Lyden, David
AU - Pietras, Kristian
AU - Blanchard, Scott C.
AU - Vincent, C. Theresa
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-019-10100-8
DO - 10.1038/s41467-019-10100-8
M3 - Article
C2 - 31068593
AN - SCOPUS:85065642970
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2110
ER -