Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease.
Nat Commun
; 10(1): 2110, 2019 05 08.
Article
em En
| MEDLINE
| ID: mdl-31068593
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ribossomos
/
Regulação Neoplásica da Expressão Gênica
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Regulação da Expressão Gênica no Desenvolvimento
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Transição Epitelial-Mesenquimal
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Pontos de Checagem da Fase G1 do Ciclo Celular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article