Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease.
Animals
Breast Neoplasms
/ genetics
Cell Differentiation
/ physiology
Cell Line, Tumor
/ transplantation
Cell Movement
/ physiology
Cell Nucleolus
/ metabolism
Chick Embryo
Chromosomal Proteins, Non-Histone
/ metabolism
DNA, Ribosomal
/ metabolism
Disease Models, Animal
Epithelial-Mesenchymal Transition
/ physiology
Female
G1 Phase Cell Cycle Checkpoints
/ physiology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
RNA, Ribosomal
/ metabolism
Ribosomes
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 05 2019
08 05 2019
Historique:
received:
21
05
2018
accepted:
16
04
2019
entrez:
10
5
2019
pubmed:
10
5
2019
medline:
14
6
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31068593
doi: 10.1038/s41467-019-10100-8
pii: 10.1038/s41467-019-10100-8
pmc: PMC6506521
doi:
Substances chimiques
Chromosomal Proteins, Non-Histone
0
DNA, Ribosomal
0
RNA, Ribosomal
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2110Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM079238
Pays : United States
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