RRC ID 57782
Author Prakash V, Carson BB, Feenstra JM, Dass RA, Sekyrova P, Hoshino A, Petersen J, Guo Y, Parks MM, Kurylo CM, Batchelder JE, Haller K, Hashimoto A, Rundqivst H, Condeelis JS, Allis CD, Drygin D, Nieto MA, Andäng M, Percipalle P, Bergh J, Adameyko I, Farrants AÖ, Hartman J, Lyden D, Pietras K, Blanchard SC, Vincent CT.
Title Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease.
Journal Nat Commun
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.
Volume 10(1)
Pages 2110
Published 2019-5-8
DOI 10.1038/s41467-019-10100-8
PII 10.1038/s41467-019-10100-8
PMID 31068593
PMC PMC6506521
MeSH Animals Breast Neoplasms / genetics Breast Neoplasms / pathology 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 Ribosomes / metabolism*
IF 11.878
Times Cited 16
Human and Animal Cells NMuMG/Fucci2(RCB2868)