| Title | Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | 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, C Allis D, Drygin D, M Nieto A, Andäng M, Percipalle P, Bergh J, Adameyko I, Farrants A-KÖstlund, Hartman J, Lyden DC, Pietras K, Blanchard SC, C Vincent T |
| Journal | Nat Commun |
| Volume | 10 |
| Issue | 1 |
| Pagination | 2110 |
| Date Published | 2019 05 08 |
| ISSN | 2041-1723 |
| Keywords | Animals, Breast Neoplasms, Cell Differentiation, Cell Line, Tumor, Cell Movement, Cell Nucleolus, Chick Embryo, Chromosomal Proteins, Non-Histone, Disease Models, Animal, DNA, Ribosomal, Epithelial-Mesenchymal Transition, Female, G1 Phase Cell Cycle Checkpoints, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Ribosomes, RNA, Ribosomal |
| 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. |
| DOI | 10.1038/s41467-019-10100-8 |
| Custom 1 | |
| Alternate Journal | Nat Commun |
| PubMed ID | 31068593 |
| PubMed Central ID | PMC6506521 |
| Grant List | R01 GM079238 / GM / NIGMS NIH HHS / United States |