The ribosome, (slow) beating heart of cancer (stem) cell

The ribosome has long been considered as a consistent molecular factory, with a rather passive role in the translation process. Recent findings have shifted this obsolete view, revealing a remarkably complex and multifaceted machinery whose role is to orchestrate spatiotemporal control of gene expression. Ribosome specialization discovery has raised the interesting possibility of the existence of its malignant counterpart, an 'oncogenic' ribosome, which may promote tumor progression. Here we weigh the arguments supporting the existence of an 'oncogenic' ribosome and evaluate its role in cancer evolution. In particular, we provide an analysis and perspective on how the ribosome may play a critical role in the acquisition and maintenance of cancer stem cell phenotype.

[1]  G. Sauvageau,et al.  Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate , 2015, Proceedings of the National Academy of Sciences.

[2]  D. Ruggero,et al.  New frontiers in translational control of the cancer genome , 2016, Nature Reviews Cancer.

[3]  R. Spriggs,et al.  A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment , 2016, Cell Death and Disease.

[4]  Stephen T. C. Wong,et al.  Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling , 2014, Proceedings of the National Academy of Sciences.

[5]  M. Biffoni,et al.  Identification and expansion of the tumorigenic lung cancer stem cell population , 2008, Cell Death and Differentiation.

[6]  Tamás Kiss,et al.  Site-Specific Pseudouridine Formation in Preribosomal RNA Is Guided by Small Nucleolar RNAs , 1997, Cell.

[7]  Chuanhao Tang,et al.  Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells. , 2016, Gene.

[8]  Andres Grosmark,et al.  RPL38, FOSL1, and UPP1 Are Predominantly Expressed in the Pancreatic Ductal Epithelium , 2005, Pancreas.

[9]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[10]  J. Dick,et al.  Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell , 1997, Nature Medicine.

[11]  J. Visvader,et al.  Cancer stem cells: current status and evolving complexities. , 2012, Cell stem cell.

[12]  Q. She,et al.  AKT and cancer--is it all mTOR? , 2006, Cancer cell.

[13]  M. Bushell,et al.  Translational regulation of gene expression during conditions of cell stress. , 2010, Molecular cell.

[14]  Jeffrey A. Magee,et al.  Haematopoietic stem cells require a highly regulated protein synthesis rate , 2014, Nature.

[15]  S. Thorgeirsson,et al.  MYC activates stem-like cell potential in hepatocarcinoma by a p53-dependent mechanism. , 2014, Cancer research.

[16]  S. Hino,et al.  Proteomic analysis of rodent ribosomes revealed heterogeneity including ribosomal proteins L10-like, L22-like 1, and L39-like. , 2010, Journal of proteome research.

[17]  J. Yewdell,et al.  Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Henkelman,et al.  Identification of human brain tumour initiating cells , 2004, Nature.

[19]  Michaela Frye,et al.  Stem cell function and stress response are controlled by protein synthesis , 2016, Nature.

[20]  G. B. Pierce,et al.  Teratocarcinogenic and tissue-forming potentials of the cell types comprising neoplastic embryoid bodies. , 1960, Laboratory investigation; a journal of technical methods and pathology.

[21]  Shu-Bing Qian,et al.  Translational reprogramming in cellular stress response , 2014, Wiley interdisciplinary reviews. RNA.

[22]  R. Espinosa,et al.  Point Mutation in Essential Genes with Loss or Mutation of the Second Allele , 2001, The Journal of experimental medicine.

[23]  D. Felsher,et al.  MYC as a regulator of ribosome biogenesis and protein synthesis , 2010, Nature Reviews Cancer.

[24]  Yumei Zhang,et al.  Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis. , 2004, Experimental cell research.

[25]  D. Tollervey,et al.  Temperature-sensitive mutations demonstrate roles for yeast fibrillarin in pre-rRNA processing, pre-rRNA methylation, and ribosome assembly , 1993, Cell.

[26]  Shuang-yin Han,et al.  Human ribosomal protein S13 promotes gastric cancer growth through down-regulating p27Kip1 , 2009, Journal of cellular and molecular medicine.

[27]  F. Papaccio,et al.  Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  Steven A. Harvey,et al.  The Ribosome Biogenesis Protein Nol9 Is Essential for Definitive Hematopoiesis and Pancreas Morphogenesis in Zebrafish , 2015, PLoS genetics.

[29]  D. Ettinger,et al.  Variable content of histaminase, L-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung. Biologic and clinical implications. , 1978, The New England journal of medicine.

[30]  Shinya Sugimoto,et al.  Visualization and targeting of LGR5+ human colon cancer stem cells , 2017, Nature.

[31]  L. Postovit,et al.  Microenvironmental regulation of cancer stem cell phenotypes. , 2012, Current stem cell research & therapy.

[32]  M. Serrano,et al.  Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis. , 2015, Cell reports.

[33]  G. Thomas,et al.  Loss of Tumor Suppressor RPL5/RPL11 Does Not Induce Cell Cycle Arrest but Impedes Proliferation Due to Reduced Ribosome Content and Translation Capacity , 2013, Molecular and Cellular Biology.

[34]  Min Wu,et al.  Alteration of RPL14 in squamous cell carcinomas and preneoplastic lesions of the esophagus. , 2006, Gene.

[35]  M Schwab,et al.  N‐myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis , 2001, The EMBO journal.

[36]  A. Elefanty,et al.  The level of the tissue-specific factor GATA-1 affects the cell-cycle machinery. , 1997, Genes and function.

[37]  Martin A. Nowak,et al.  Mutations driving CLL and their evolution in progression and relapse , 2015, Nature.

[38]  L. Comai,et al.  Repression of RNA Polymerase I Transcription by the Tumor Suppressor p53 , 2000, Molecular and Cellular Biology.

[39]  M. Frank,et al.  Antitumor Immunity and Cancer Stem Cells , 2009, Annals of the New York Academy of Sciences.

[40]  H. Tschochner,et al.  Analysis of the in vivo assembly pathway of eukaryotic 40S ribosomal proteins. , 2007, Molecular cell.

[41]  J. Dick,et al.  A human colon cancer cell capable of initiating tumour growth in immunodeficient mice , 2007, Nature.

[42]  Nicholas T. Ingolia,et al.  The translational landscape of mTOR signalling steers cancer initiation and metastasis , 2012, Nature.

[43]  E. Lander,et al.  Altered translation of GATA1 in Diamond-Blackfan anemia , 2014, Nature Medicine.

[44]  B. Paw,et al.  The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability , 2015, Science Signaling.

[45]  L. Aaltonen,et al.  High Frequency of RPL22 Mutations in Microsatellite‐Unstable Colorectal and Endometrial Tumors , 2014, Human mutation.

[46]  Paul A. Townsend,et al.  Targeting tumor-initiating cells: Eliminating anabolic cancer stem cells with inhibitors of protein synthesis or by mimicking caloric restriction , 2015, Oncotarget.

[47]  G. Fichant,et al.  Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits , 2010, The Journal of cell biology.

[48]  S. Morrison,et al.  Heterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution , 2009, Cell.

[49]  P. Sorensen,et al.  Stress-mediated translational control in cancer cells. , 2015, Biochimica et biophysica acta.

[50]  J. Tabernero,et al.  Targeting the PI3K/Akt/mTOR Pathway – Beyond Rapalogs , 2010, Oncotarget.

[51]  H. Li,et al.  Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells , 2006, Oncogene.

[52]  J. Yewdell,et al.  RNA Binding Targets Aminoacyl-tRNA Synthetases to Translating Ribosomes* , 2011, The Journal of Biological Chemistry.

[53]  E. Airoldi,et al.  Differential Stoichiometry among Core Ribosomal Proteins , 2014, bioRxiv.

[54]  J. Ladenson,et al.  The role of human ribosomal proteins in the maturation of rRNA and ribosome production. , 2008, RNA.

[55]  Inge M. N. Wortel,et al.  Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells , 2017, Trends in Endocrinology & Metabolism.

[56]  J. Dinman Pathways to Specialized Ribosomes: The Brussels Lecture. , 2016, Journal of Molecular Biology.

[57]  I. Thompson,et al.  Elevated snoRNA biogenesis is essential in breast cancer , 2014, Oncogene.

[58]  W. Ahn,et al.  Identification of differentially expressed genes using annealing control primer-based GeneFishing in human squamous cell cervical carcinoma. , 2007, Clinical oncology (Royal College of Radiologists (Great Britain)).

[59]  Davide Ruggero,et al.  New frontiers in translational control of the cancer genome , 2016, Nature Reviews Cancer.

[60]  Dae‐Ghon Kim,et al.  Over‐expression of the ribosomal protein L36a gene is associated with cellular proliferation in hepatocellular carcinoma , 2004, Hepatology.

[61]  D. Drummond,et al.  Correction: A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus , 2015, PLoS biology.

[62]  Sergey Melnikov,et al.  The Structure of the Eukaryotic Ribosome at 3.0 Å Resolution , 2011, Science.

[63]  J. Dinman,et al.  Ribosomopathies and the paradox of cellular hypo- to hyperproliferation. , 2015, Blood.

[64]  C. Stumpf,et al.  The cancerous translation apparatus. , 2011, Current opinion in genetics & development.

[65]  Xiang Zhou,et al.  Ribosomal proteins: functions beyond the ribosome. , 2015, Journal of molecular cell biology.

[66]  A. Ferrando,et al.  Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL , 2013, Nature Medicine.

[67]  D. Tollervey,et al.  Ribosome synthesis in Saccharomyces cerevisiae. , 1999, Annual review of genetics.

[68]  Daniel Birnbaum,et al.  ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. , 2007, Cell stem cell.

[69]  D. Corbeil,et al.  CD133 as a biomarker for putative cancer stem cells in solid tumours: limitations, problems and challenges , 2013, The Journal of pathology.

[70]  Larry A. Sklar,et al.  Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia , 2016, Cell.

[71]  M. Tyers,et al.  A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. , 2004, Genes & development.

[72]  V. Marcel,et al.  Ribosomal RNA Methylation and Cancer , 2015 .

[73]  P. Dalerba,et al.  Identification of pancreatic cancer stem cells. , 2006, Cancer research.

[74]  L. Ricci-Vitiani,et al.  Identification and expansion of human colon-cancer-initiating cells , 2007, Nature.

[75]  A. Hinnebusch,et al.  Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets , 2009, Cell.

[76]  S. Thompson,et al.  Ribosomal Protein S25 Dependency Reveals a Common Mechanism for Diverse Internal Ribosome Entry Sites and Ribosome Shunting , 2012, Molecular and Cellular Biology.

[77]  R. Aebersold,et al.  Selected reaction monitoring–based proteomics: workflows, potential, pitfalls and future directions , 2012, Nature Methods.

[78]  Pierre-Emmanuel Gleizes,et al.  Roles of eukaryotic ribosomal proteins in maturation and transport of pre-18S rRNA and ribosome function. , 2005, Molecular cell.

[79]  Melissa J. Moore,et al.  Redefining the Translational Status of 80S Monosomes , 2016, Cell.

[80]  A. Cheung,et al.  Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential , 2007, Leukemia.

[81]  J. Becker,et al.  Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells: selective escape of CD44high/CD24low/HER2low breast cancer stem cells. , 2009, Cancer research.

[82]  Atique U. Ahmed,et al.  Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance , 2016, Journal of stem cell research & therapy.

[83]  D. Elder,et al.  A tumorigenic subpopulation with stem cell properties in melanomas. , 2005, Cancer research.

[84]  Hui Wang,et al.  c-Myc Is Required for Maintenance of Glioma Cancer Stem Cells , 2008, PloS one.

[85]  M van Duin,et al.  RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response , 2016, Leukemia.

[86]  H. Zhang,et al.  Overexpression of Ribosomal RNA in the Development of Human Cervical Cancer Is Associated with rDNA Promoter Hypomethylation , 2016, PloS one.

[87]  C. Heeschen,et al.  MYC/PGC-1α Balance Determines the Metabolic Phenotype and Plasticity of Pancreatic Cancer Stem Cells. , 2015, Cell metabolism.

[88]  Shifeng Xue,et al.  Specialized ribosomes: a new frontier in gene regulation and organismal biology , 2012, Nature Reviews Molecular Cell Biology.

[89]  Micheline Fromont-Racine,et al.  Ribosome assembly in eukaryotes. , 2003, Gene.

[90]  D. Lafontaine,et al.  'View From A Bridge': A New Perspective on Eukaryotic rRNA Base Modification. , 2015, Trends in biochemical sciences.

[91]  C. Foster,et al.  Ribosomal Protein L19 Is a Prognostic Marker for Human Prostate Cancer , 2006, Clinical Cancer Research.

[92]  Huiyu Xu,et al.  ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver. , 2015, Blood.

[93]  H. Noller,et al.  Unusual resistance of peptidyl transferase to protein extraction procedures. , 1992, Science.

[94]  A. Regev,et al.  An embryonic stem cell–like gene expression signature in poorly differentiated aggressive human tumors , 2008, Nature Genetics.

[95]  M. Dai,et al.  Inhibition of c‐Myc activity by ribosomal protein L11 , 2007, The EMBO journal.

[96]  C. Koh,et al.  Overexpression of ribosomal RNA in prostate cancer is common but not linked to rDNA promoter hypomethylation , 2011, Oncogene.

[97]  Michael Margaliot,et al.  On the Ribosomal Density that Maximizes Protein Translation Rate , 2016, PloS one.

[98]  B. Ebert,et al.  Ribosomopathies: human disorders of ribosome dysfunction. , 2010, Blood.

[99]  Albert Kriegner,et al.  Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan , 2015, Nature Communications.

[100]  J. Sayre,et al.  In vivo imaging, tracking, and targeting of cancer stem cells. , 2009, Journal of the National Cancer Institute.

[101]  F. Jiang,et al.  Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis , 2011, Oncogene.

[102]  P. Goodfellow,et al.  Frequent mutations in the RPL22 gene and its clinical and functional implications. , 2013, Gynecologic oncology.

[103]  William Elison,et al.  Line , 2017, The Craft of Poetry.

[104]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[105]  C. Proud,et al.  mTORC1 signaling controls multiple steps in ribosome biogenesis. , 2014, Seminars in cell & developmental biology.

[106]  C. Cavaliere,et al.  Detection and Characterization of CD133+ Cancer Stem Cells in Human Solid Tumours , 2008, PloS one.

[107]  A. Pelava,et al.  The importance of ribosome production, and the 5S RNP–MDM2 pathway, in health and disease , 2016, Biochemical Society transactions.

[108]  B. Paw,et al.  L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. , 2012, Blood.

[109]  M. Muratani,et al.  NOTCH1-mutated chronic lymphocytic leukemia cells are characterized by a MYC-related overexpression of nucleophosmin 1 and ribosome-associated components , 2017, Leukemia.

[110]  Yohann Couté,et al.  Evidence for rRNA 2′-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes , 2017, Proceedings of the National Academy of Sciences.

[111]  S. Nelson,et al.  Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients , 2015, PloS one.

[112]  J. Ni,et al.  Small Nucleolar RNAs Direct Site-Specific Synthesis of Pseudouridine in Ribosomal RNA , 1997, Cell.

[113]  P. Pandolfi,et al.  The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis , 2004, Nature Medicine.

[114]  H. Bielka,et al.  On the stoichiometry of proteins in the small ribosomal subunit of hepatoma ascites cells , 1976, FEBS letters.

[115]  D. Lafontaine,et al.  Noncoding RNAs in eukaryotic ribosome biogenesis and function , 2015, Nature Structural &Molecular Biology.

[116]  Nancy Hopkins,et al.  Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish , 2004, PLoS biology.

[117]  S. Hardy The stoichiometry of the ribosomal proteins of Escherichia coli , 1975, Molecular and General Genetics MGG.

[118]  Orly L. Wapinski,et al.  A self-limiting switch based on translational control regulates the transition from proliferation to differentiation in an adult stem cell lineage. , 2012, Cell stem cell.

[119]  K. Dutton-Regester,et al.  A highly recurrent RPS27 5'UTR mutation in melanoma , 2014, Oncotarget.

[120]  D. Drummond,et al.  A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus , 2014, PLoS biology.

[121]  H. Clevers,et al.  Identification of stem cells in small intestine and colon by marker gene Lgr5 , 2007, Nature.

[122]  I. van Mechelen,et al.  Using Ribosomal Protein Genes as Reference: A Tale of Caution , 2008, PloS one.

[123]  G. Viglietto,et al.  The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer. , 2009, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[124]  Niranjan Nagarajan,et al.  Whole-genome reconstruction and mutational signatures in gastric cancer , 2012, Genome Biology.

[125]  T. Hibi,et al.  CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence , 2013, British Journal of Cancer.

[126]  W. Held,et al.  Reconstitution of Escherichia coli 30 S ribosomal subunits from purified molecular components. , 1973, The Journal of biological chemistry.

[127]  Tamás Kiss,et al.  Site-Specific Ribose Methylation of Preribosomal RNA: A Novel Function for Small Nucleolar RNAs , 1996, Cell.

[128]  K. Stamatopoulos,et al.  Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations. , 2016, Blood.

[129]  G. Edelman,et al.  The ribosome filter hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[130]  Jianmin Wang,et al.  Homoharringtonine and omacetaxine for myeloid hematological malignancies , 2014, Journal of Hematology & Oncology.

[131]  Davide Ruggero,et al.  rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. , 2011, Molecular cell.

[132]  A. Beggs,et al.  Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice , 2016, Journal of Cancer.

[133]  T. von der Haar,et al.  Mathematical and Computational Modelling of Ribosomal Movement and Protein Synthesis: an overview , 2012, Computational and structural biotechnology journal.

[134]  C. Heeschen,et al.  Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. , 2007, Cell stem cell.

[135]  J. Plotkin,et al.  Rate-Limiting Steps in Yeast Protein Translation , 2013, Cell.

[136]  Laura Fancello,et al.  The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types , 2017, Oncotarget.

[137]  A. Richardson,et al.  Characterization of a variant-producing tumor cell line from a heterogeneous strain BALB/cfC3H mouse mammary tumor. , 1981, Cancer research.

[138]  P. Mischel,et al.  Tumor cells with low proteasome subunit expression predict overall survival in head and neck cancer patients , 2014, BMC Cancer.

[139]  J. Soudet,et al.  The post-transcriptional steps of eukaryotic ribosome biogenesis , 2008, Cellular and Molecular Life Sciences.

[140]  Ed Hurt,et al.  Pre-ribosomes on the road from the nucleolus to the cytoplasm. , 2003, Trends in cell biology.

[141]  Varun Gupta,et al.  Ribosome-omics of the human ribosome , 2014, RNA.

[142]  Davide Ruggero,et al.  Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency , 2008, Nature.

[143]  Francesco Piazza,et al.  Dyskeratosis Congenita and Cancer in Mice Deficient in Ribosomal RNA Modification , 2003, Science.

[144]  Feng Jiang,et al.  Small nucleolar RNA signatures of lung tumor-initiating cells , 2014, Molecular Cancer.

[145]  Arlen W. Johnson,et al.  Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis , 2014, Proceedings of the National Academy of Sciences.

[146]  Lil Pabon,et al.  A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation. , 2008, Cell stem cell.

[147]  S. Bryant,et al.  Analysis of the pattern of QM expression during mouse development. , 1999, Differentiation; research in biological diversity.

[148]  R. Green,et al.  Ribosomopathies: There’s strength in numbers , 2017, Science.

[149]  J. Saurin,et al.  p53 Acts as a Safeguard of Translational Control by Regulating Fibrillarin and rRNA Methylation in Cancer , 2013, Cancer Cell.

[150]  F. Sotgia,et al.  Cancer stem cell metabolism , 2016, Breast Cancer Research.

[151]  B. Alman,et al.  Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. , 2007, Cancer research.

[152]  J. Warner,et al.  The economics of ribosome biosynthesis in yeast. , 1999, Trends in biochemical sciences.

[153]  Z. Luthey-Schulten,et al.  Protein-guided RNA dynamics during early ribosome assembly , 2014, Nature.

[154]  N. Maitland,et al.  Prospective identification of tumorigenic prostate cancer stem cells. , 2005, Cancer research.

[155]  R. Horos,et al.  Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts. , 2012, Blood.

[156]  Y. Shi,et al.  Therapeutic potential of targeting IRES-dependent c-myc translation in multiple myeloma cells during ER stress , 2015, Oncogene.

[157]  Wei Xu,et al.  Impaired Control of IRES-Mediated Translation in X-Linked Dyskeratosis Congenita , 2006, Science.

[158]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[159]  D. Ruggero The role of Myc-induced protein synthesis in cancer. , 2009, Cancer research.

[160]  Shifeng Xue,et al.  Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning , 2011, Cell.

[161]  M. Buszczak,et al.  Changes in rRNA Transcription Influence Proliferation and Cell Fate Within a Stem Cell Lineage , 2014, Science.

[162]  I. Weissman,et al.  Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma , 2007, Proceedings of the National Academy of Sciences.

[163]  K. Fujii,et al.  Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide. , 2017, Molecular cell.

[164]  Jan Paul Medema,et al.  Cancer stem cells: The challenges ahead , 2013, Nature Cell Biology.

[165]  Patrick Linder,et al.  Protein trans-Acting Factors Involved in Ribosome Biogenesis in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[166]  I. Stansfield,et al.  Ribosome recycling induces optimal translation rate at low ribosomal availability , 2014, Journal of The Royal Society Interface.

[167]  M. Schapira,et al.  Regulated translation initiation controls stress-induced gene expression in mammalian cells. , 2000, Molecular cell.

[168]  L. Montanaro,et al.  The importance of being (slightly) modified: The role of rRNA editing on gene expression control and its connections with cancer. , 2016, Biochimica et biophysica acta.

[169]  M. Bohnsack,et al.  The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA , 2012, Wiley interdisciplinary reviews. RNA.

[170]  H. Weber Stoichiometric measurements of 30S and 50S ribosomal proteins from Escherichia coli , 2004, Molecular and General Genetics MGG.

[171]  N. Sonenberg,et al.  Targeting the translation machinery in cancer , 2015, Nature Reviews Drug Discovery.

[172]  J. Jonkers,et al.  p53 deficiency induces cancer stem cell pool expansion in a mouse model of triple-negative breast tumors , 2017, Oncogene.

[173]  MicroRNA-7641 is a regulator of ribosomal proteins and a promising targeting factor to improve the efficacy of cancer therapy , 2017, Scientific Reports.

[174]  Michael Margaliot,et al.  A model for competition for ribosomes in the cell , 2015, Journal of The Royal Society Interface.

[175]  Sergey V. Melnikov,et al.  The structure of the eukaryotic ribosome at 3.0 angstrom resolution. , 2011 .

[176]  A. Look,et al.  Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. , 2012, Blood.

[177]  M. Serrano,et al.  Rplp1 bypasses replicative senescence and contributes to transformation. , 2009, Experimental cell research.

[178]  P. Pandolfi,et al.  Does the ribosome translate cancer? , 2003, Nature Reviews Cancer.

[179]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[180]  C. Bellodi,et al.  Deregulation of oncogene‐induced senescence and p53 translational control in X‐linked dyskeratosis congenita , 2010, The EMBO journal.

[181]  Barbara M. Bakker,et al.  How Molecular Competition Influences Fluxes in Gene Expression Networks , 2011, PloS one.

[182]  Howard Y. Chang,et al.  The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity , 2017, Cell.

[183]  X. Zhang,et al.  Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients , 2017, Oncogene.

[184]  R. Lehmann,et al.  Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation. , 2016, Cell stem cell.

[185]  S. Formenti,et al.  Translational control in cancer , 2010, Nature Reviews Cancer.

[186]  R. Weinberg,et al.  Cell plasticity and heterogeneity in cancer. , 2013, Clinical chemistry.

[187]  Hani S. Zaher,et al.  Fidelity at the Molecular Level: Lessons from Protein Synthesis , 2009, Cell.

[188]  Tzong-Shiue Yu,et al.  A restricted cell population propagates glioblastoma growth after chemotherapy , 2012 .

[189]  S. Lowe,et al.  Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a , 1997, Cell.

[190]  Chiara Romualdi,et al.  Differential expression of genes coding for ribosomal proteins in different human tissues , 2001, Bioinform..

[191]  S. Morley,et al.  Translation initiation factors and active sites of protein synthesis co-localize at the leading edge of migrating fibroblasts. , 2011, The Biochemical journal.

[192]  Xinbing Sui,et al.  Oncogenic mechanisms of Lin28 in breast cancer: new functions and therapeutic opportunities , 2017, Oncotarget.

[193]  Stein Aerts,et al.  Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia , 2012, Nature Genetics.

[194]  S. Armstrong,et al.  Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations , 2017, EMBO molecular medicine.

[195]  P. Rosenberg,et al.  Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. , 2012, Blood.

[196]  M. Toyota,et al.  Activation of the ribosomal protein L13 gene in human gastrointestinal cancer. , 2006, International journal of molecular medicine.

[197]  J. Dinman,et al.  How Ribosomes Translate Cancer. , 2017, Cancer discovery.

[198]  G. Thomas,et al.  Suprainduction of p53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint. , 2012, Genes & development.

[199]  P. Rudland,et al.  A possible mammary stem cell line , 1978, Cell.

[200]  Harvey F. Lodish,et al.  Model for the regulation of mRNA translation applied to haemoglobin synthesis , 1974, Nature.

[201]  K. Zeller,et al.  Alterations in nucleolar structure and gene expression programs in prostatic neoplasia are driven by the MYC oncogene. , 2011, The American journal of pathology.

[202]  J. Tower Stress and stem cells , 2012, Wiley interdisciplinary reviews. Developmental biology.

[203]  Mihaela Zavolan,et al.  Patterns of ribosomal protein expression specify normal and malignant human cells , 2016, Genome Biology.