Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer

Journal of Experimental Medicine

Volumn 213, Issue 11, 2016, Pages 2503-2523

  Delaunay, Sylvain ^a,c,f   Rapino, Francesca ^a,c,f   Tharun, Lars ^g   Zhou, Zhaoli ^a,c,f   Heukamp, Lukas ^g   Termathe, Martin ^h,i   Shostak, Kateryna ^b,c,f   Klevernic, Iva ^b,c,f   Florin, Alexandra ^g   Desmecht, Hadrien ^b,c,f   Desmet, Christophe J ^d,f   Nguyen, Laurent ^e,f   Leidel, Sebastian A ^h,i   Willis, Anne E ^j   Büttner, Reinhard ^g   Chariot, Alain ^b,c,f,k   Close, Pierre ^a,c,f  

^a Laboratory of Cancer Signaling   (Belgium)

^b Lab of Med Chem and Hum Genetics   (Belgium)

^c GIGA Molecular Biology in Diseases   (Belgium)

^d GIGA Research Institute   (Belgium)

^e GIGA Neurosiences   (Belgium)

^f UNIVERSITY OF LIÈGE   (Belgium)

^g UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^h MAX PLANCK INSTITUTE FOR MOLECULAR BIOMEDICINE   (Germany)

ⁱ UNIVERSITY OF MÜNSTER   (Germany)

^j MRC TOXICOLOGY UNIT   (United Kingdom)

^k Walloon Excellence in Life Sciences and Biotechnology (WELBIO)   (Belgium)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ELONGATION FACTOR; ELONGATOR COMPLEX PROTEIN 3; ENZYME; LYMPHOID ENHANCER FACTOR 1; ONCOPROTEIN; PROTEIN DEK; THIOURIDYLASE 1; THIOURIDYLASE 2; TRANSFER RNA; UNCLASSIFIED DRUG; 5-CARBOMETHOXYMETHYL-2-THIOURIDINE; DEK PROTEIN, HUMAN; ELP3 PROTEIN, HUMAN; HISTONE ACETYLTRANSFERASE; INTERNAL RIBOSOME ENTRY SITE; NERVE PROTEIN; NONHISTONE PROTEIN; THIOURIDINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL; CANCER GROWTH; CELL INVASION; CELL MIGRATION; CHEMICAL MODIFICATION; CODON; CONTROLLED STUDY; HUMAN; HUMAN TISSUE; INTERNAL RIBOSOME ENTRY SITE; LUNG METASTASIS; METASTASIS POTENTIAL; METASTATIC BREAST CANCER; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; TUMOR INVASION; UPREGULATION; ANALOGS AND DERIVATIVES; ANIMAL; BIOLOGICAL MODEL; BREAST TUMOR; CELL MOTION; ENZYMOLOGY; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; MCF-7 CELL LINE; METABOLISM; METASTASIS; PATHOLOGY;

ANIMALS; BREAST NEOPLASMS; CELL MOVEMENT; CHROMOSOMAL PROTEINS, NON-HISTONE; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONE ACETYLTRANSFERASES; HUMANS; INTERNAL RIBOSOME ENTRY SITES; LYMPHOID ENHANCER-BINDING FACTOR 1; MCF-7 CELLS; MICE; MODELS, BIOLOGICAL; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; NERVE TISSUE PROTEINS; ONCOGENE PROTEINS; PROTEIN BIOSYNTHESIS; RNA, TRANSFER; THIOURIDINE; UP-REGULATION;

EID: 85014960372     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20160397     Document Type: Article

References (78)

1. Anastas, J.N., and R.T. Moon. 2013. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer. 13:11-26. http ://dx .doi .org /10 .1038 /nrc3419
2. Bauer, F., A. Matsuyama, J. Candiracci, M. Dieu, J. Scheliga, D.A. Wolf, M' Yoshida, and D. Hermand. 2012. Translational control of cell division by Elongator. Cell Reports. 1:424-433. http ://dx .doi .org /10 .1016 /j .celrep .2012 .04 .001
3. Björk, G.R., B. Huang, O.P. Persson, and A.S. Byström. 2007. A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast. RNA. 13:1245-1255. http ://dx .doi .org /10 .1261 /rna .558707
4. Cai, J., H. Guan, L. Fang, Y. Yang, X. Zhu, J. Yuan, J. Wu, and M. Li. 2013' MicroRNA-374a activates Wnt/ß-catenin signaling to promote breast cancer metastasis. J. Clin. Invest. 123:566-579. http ://dx .doi .org /10 .1172 /JCI65871
5. Chen, C., S. Tuck, and A.S. Byström. 2009. Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants. PLoS Genet. 5:e1000561' http ://dx .doi .org /10 .1371 /journal .pgen .1000561
6. Cheung, K.J., E. Gabrielson, Z. Werb, and A.J. Ewald. 2013. Collective invasion in breast cancer requires a conserved basal epithelial program' Cell. 155:1639-1651. http ://dx .doi .org /10 .1016 /j .cell .2013 .11 .029
7. Close, P., N. Hawkes, I. Cornez, C. Creppe, C.A. Lambert, B. Rogister, U. Siebenlist, M.P. Merville, S.A. Slaugenhaupt, V. Bours, et al. 2006' Transcription impairment and cell migration defects in elongatordepleted cells: implication for familial dysautonomia. Mol. Cell. 22:521- 531. http ://dx .doi .org /10 .1016 /j .molcel .2006 .04 .017
8. Close, P., M. Gillard, A. Ladang, Z. Jiang, J. Papuga, N. Hawkes, L. Nguyen, J.P. Chapelle, F. Bouillenne, J. Svejstrup, et al. 2012. DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator. J. Biol. Chem. 287:32535-32545. http ://dx .doi .org /10 .1074 /jbc .M112 .402727
9. Creppe, C., L. Malinouskaya, M.L. Volvert, M. Gillard, P. Close, O. Malaise, S' Laguesse, I. Cornez, S. Rahmouni, S. Ormenese, et al. 2009. Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell. 136:551-564. http ://dx .doi .org /10 .1016 /j .cell .2008 .11 .043
10. Dewez, M., F. Bauer, M. Dieu, M. Raes, J. Vandenhaute, and D. Hermand. 2008' The conserved Wobble uridine tRNA thiolase Ctu1-Ctu2 is required to maintain genome integrity. Proc. Natl. Acad. Sci. USA. 105:5459-5464' http ://dx .doi .org /10 .1073 /pnas .0709404105
11. El Yacoubi, B., M. Bailly, and V. de Crécy-Lagard. 2012. Biosynthesis and function of posttranscriptional modifications of transfer RNAs. Annu' Rev. Genet. 46:69-95. http ://dx .doi .org /10 .1146 /annurev -genet -110711 -155641
12. Esberg, A., B. Huang, M.J.O. Johansson, and A.S. Byström. 2006. Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol. Cell. 24:139-148. http :// dx .doi .org /10 .1016 /j .molcel .2006 .07 .031
13. Fernández-Vázquez, J., I. Vargas-Pérez, M. Sansó, K. Buhne, M. Carmona, E. Paulo, D. Hermand, M. Rodríguez-Gabriel, J. Ayté, S. Leidel, and E' Hidalgo. 2013. Modification of tRNA(Lys) UUU by elongator is essential for efficient translation of stress mRNAs. PLoS Genet. 9:e1003647. http ://dx .doi .org /10 .1371 /journal .pgen .1003647
14. Filipits, M., M. Rudas, R. Jakesz, P. Dubsky, F. Fitzal, C.F. Singer, O. Dietze, R' Greil, A. Jelen, P. Sevelda, et al. EP Investigators. 2011. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin. Cancer Res. 17:6012-6020. http ://dx .doi .org /10 .1158 /1078 -0432 .CCR -11 -0926
15. Goodarzi, H., H.C.B. Nguyen, S. Zhang, B.D. Dill, H. Molina, and S.F' Tavazoie. 2016. Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression. Cell. 165:1416-1427. http ://dx .doi .org /10 .1016 /j .cell .2016 .05 .046
16. Grewal, S.S. 2015. Why should cancer biologists care about tRNAs? tRNA synthesis, mRNA translation and the control of growth. Biochim. Biophys' Acta. 1849:898-907. http ://dx .doi .org /10 .1016 /j .bbagrm .2014 .12 .005
17. Guttilla, I.K., K.N. Phoenix, X. Hong, J.S. Tirnauer, K.P. Claffey, and B.A' White. 2012. Prolonged mammosphere culture of MCF-7 cells induces an EMT and repression of the estrogen receptor by microRNAs. Breast Cancer Res. Treat. 132:75-85. http ://dx .doi .org /10 .1007 /s10549 -011 -1534 -y
18. Guy, C.T., R.D. Cardiff, and W.J. Muller. 1992. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol. Cell. Biol. 12:954-961. http :// dx .doi .org /10 .1128 /MCB .12 .3 .954
19. Huang, B., J. Lu, and A.S. Byström. 2008. A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae' RNA. 14:2183-2194. http ://dx .doi .org /10 .1261 /rna .1184108
20. Huang, F.-I., Y.-L. Chen, C.-N. Chang, R.-H. Yuan, and Y.-M. Jeng. 2012' Hepatocyte growth factor activates Wnt pathway by transcriptional activation of LEF1 to facilitate tumor invasion. Carcinogenesis. 33:1142- 1148. http ://dx .doi .org /10 .1093 /carcin /bgs131
21. Jang, G.-B., J.-Y. Kim, S.-D. Cho, K.-S. Park, J.-Y. Jung, H.-Y. Lee, I.-S. Hong, and J.-S. Nam. 2015. Blockade of Wnt/ß-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype. Sci. Rep' 5:12465. http ://dx .doi .org /10 .1038 /srep12465
22. Jimenez, J., G.M. Jang, B.L. Semler, and M.L. Waterman. 2005. An internal ribosome entry site mediates translation of lymphoid enhancer factor-1' RNA. 11:1385-1399. http ://dx .doi .org /10 .1261 /rna .7226105
23. Johansen, L.D., T. Naumanen, A. Knudsen, N. Westerlund, I. Gromova, M' Junttila, C. Nielsen, T. Bøttzauw, A. Tolkovsky, J. Westermarck, et al. 2008' IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration. J. Cell Sci. 121:854-864' http ://dx .doi .org /10 .1242 /jcs .013722
24. Kalhor, H.R., and S. Clarke. 2003. Novel methyltransferase for modified uridine residues at the wobble position of tRNA. Mol. Cell. Biol' 23:9283-9292. http ://dx .doi .org /10 .1128 /MCB .23 .24 .9283 -9292 .2003
25. Kappes, F., K. Burger, M. Baack, F.O. Fackelmayer, and C. Gruss. 2001' Subcellular localization of the human proto-oncogene protein DEK' J. Biol. Chem. 276:26317-26323. http ://dx .doi .org /10 .1074 /jbc .M100162200
26. Karlsborn, T., H. Tükenmez, A.K.M.F. Mahmud, F. Xu, H. Xu, and A.S' Byström. 2015. Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes. RNA Biol. 11:1519-1528. http :// dx .doi .org /10 .4161 /15476286 .2014 .992276
27. Khodadoust, M.S., M. Verhaegen, F. Kappes, E. Riveiro-Falkenbach, J.C' Cigudosa, D.S.L. Kim, A.M. Chinnaiyan, D.M. Markovitz, and M.S' Soengas. 2009. Melanoma proliferation and chemoresistance controlled by the DEK oncogene. Cancer Res. 69:6405-6413. http ://dx .doi .org /10 .1158 /0008 -5472 .CAN -09 -1063
28. Klein, C.A. 2013. Selection and adaptation during metastatic cancer progression. Nature. 501:365-372. http ://dx .doi .org /10 .1038 / nature12628
29. Kondoh, N., T. Wakatsuki, A. Ryo, A. Hada, T. Aihara, S. Horiuchi, N. Goseki, O. Matsubara, K. Takenaka, M. Shichita, et al. 1999. Identification and characterization of genes associated with human hepatocellular carcinogenesis' Cancer Res. 59:4990-4996'
30. Ladang, A., F. Rapino, L.C. Heukamp, L. Tharun, K. Shostak, D. Hermand, S' Delaunay, I. Klevernic, Z. Jiang, N. Jacques, et al. 2015. Elp3 drives Wntdependent tumor initiation and regeneration in the intestine. J. Exp. Med' 212:2057-2075. http ://dx .doi .org /10 .1084 /jem .20142288
31. LaGamba, D., A. Nawshad, and E.D. Hay. 2005. Microarray analysis of gene expression during epithelial-mesenchymal transformation. Dev. Dyn' 234:132-142. http ://dx .doi .org /10 .1002 /dvdy .20489
32. Laguesse, S., C. Creppe, D.D. Nedialkova, P.-P. Prévot, L. Borgs, S. Huysseune, B. Franco, G. Duysens, N. Krusy, G. Lee, et al. 2015. A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis' Dev. Cell. 35:553-567. http ://dx .doi .org /10 .1016 /j .devcel .2015 .11 .005
33. Lee, G., E.P. Papapetrou, H. Kim, S.M. Chambers, M.J. Tomishima, C.A' Fasano, Y.M. Ganat, J. Menon, F. Shimizu, A. Viale, et al. 2009. Modelling pathogenesis and treatment of familial dysautonomia using patientspecific iPSCs. Nature. 461:402-406. http ://dx .doi .org /10 .1038 / nature08320
34. Le Hir, H., D. Gatfield, E. Izaurralde, and M.J. Moore. 2001. The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J' 20:4987-4997. http ://dx .doi .org /10 .1093 /emboj /20 .17 .4987
35. Leidel, S., P.G.A. Pedrioli, T. Bucher, R. Brost, M. Costanzo, A. Schmidt, R' Aebersold, C. Boone, K. Hofmann, and M. Peter. 2009. Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA. Nature. 458:228-232. http ://dx .doi .org /10 .1038 / nature07643
36. Lin, E.Y., J.G. Jones, P. Li, L. Zhu, K.D. Whitney, W.J. Muller, and J.W. Pollard' 2003. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases' Am. J. Pathol. 163:2113-2126. http ://dx .doi .org /10 .1016 /S0002 -9440(10)63568 -7
37. Lin, F.J., L. Shen, C.W. Jang, P.O. Falnes, and Y. Zhang. 2013. Ikbkap/Elp1 deficiency causes male infertility by disrupting meiotic progression. PLoS Genet. 9:e1003516. http ://dx .doi .org /10 .1371 /journal .pgen .1003516
38. Liu, S., X. Wang, F. Sun, J. Kong, Z. Li, and Z. Lin. 2012. DEK overexpression is correlated with the clinical features of breast cancer. Pathol. Int' 62:176-181. http ://dx .doi .org /10 .1111 /j .1440 -1827 .2011 .02775 .x
39. Malanchi, I. 2012. Abstract SY28-02: Interactions between cancer stem cells and their niche govern metastatic colonization. Cancer Res. 72(8 Supplement):1-12. http ://dx .doi .org /10 .1158 /1538 -7445 .AM2012 -SY28 -02
40. Massagué, J. 2008. TGFbeta in Cancer. Cell. 134:215-230. http ://dx .doi .org /10 .1016 /j .cell .2008 .07 .001
41. McGarvey, T., E. Rosonina, S. McCracken, Q. Li, R. Arnaout, E. Mientjes, J.A. Nickerson, D. Awrey, J. Greenblatt, G. Grosveld, and B.J. Blencowe' 2000. The acute myeloid leukemia-associated protein, DEK, forms a splicing-dependent interaction with exon-product complexes. J. Cell Biol. 150:309-320. http ://dx .doi .org /10 .1083 /jcb .150 .2 .309
42. Medici, D., E.D. Hay, and D.A. Goodenough. 2006. Cooperation between snail and LEF-1 transcription factors is essential for TGF-beta1-induced epithelial-mesenchymal transition. Mol. Biol. Cell. 17:1871-1879. http :// dx .doi .org /10 .1091 /mbc .E05 -08 -0767
43. Morfoisse, F., A. Kuchnio, C. Frainay, A. Gomez-Brouchet, M.B. Delisle, S' Marzi, A.C. Helfer, F. Hantelys, F. Pujol, J. Guillermet-Guibert, et al. 2014. Hypoxia induces VEGF-C expression in metastatic tumor cells via a HIF-1a-independent translation-mediated mechanism. Cell Reports' 6:155-167. http ://dx .doi .org /10 .1016 /j .celrep .2013 .12 .011
44. Nakai, Y., N. Umeda, T. Suzuki, M. Nakai, H. Hayashi, K. Watanabe, and H' Kagamiyama. 2004. Yeast Nfs1p is involved in thio-modification of both mitochondrial and cytoplasmic tRNAs. J. Biol. Chem. 279:12363-12368' http ://dx .doi .org /10 .1074 /jbc .M312448200
45. Nakai, Y., M. Nakai, and H. Hayashi. 2008. Thio-modification of yeast cytosolic tRNA requires a ubiquitin-related system that resembles bacterial sulfur transfer systems. J. Biol. Chem. 283:27469-27476. http :// dx .doi .org /10 .1074 /jbc .M804043200
46. Nawshad, A., and E.D. Hay. 2003. TGFbeta3 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate development. J. Cell Biol. 163:1291-1301. http :// dx .doi .org /10 .1083 /jcb .200306024
47. Nedialkova, D.D., and S.A. Leidel. 2015. Optimization of Codon Translation Rates via tRNA Modifications Maintains Proteome Integrity. Cell' 161:1606-1618. http ://dx .doi .org /10 .1016 /j .cell .2015 .05 .022
48. Nguyen, A., A. Rosner, T. Milovanovic, C. Hope, K. Planutis, B. Saha, B' Chaiwun, F. Lin, S.A. Imam, J.L. Marsh, and R.F. Holcombe. 2005. Wnt pathway component LEF1 mediates tumor cell invasion and is expressed in human and murine breast cancers lacking ErbB2 (her-2/neu) overexpression' Int. J. Oncol. 27:949-956'
49. Nguyen, D.X., A.C. Chiang, X.H.F. Zhang, J.Y. Kim, M.G. Kris, M. Ladanyi, W.L. Gerald, and J. Massagué. 2009. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell. 138:51-62' http ://dx .doi .org /10 .1016 /j .cell .2009 .04 .030
50. Noma, A., Y. Sakaguchi, and T. Suzuki. 2009. Mechanistic characterization of the sulfur-relay system for eukaryotic 2-thiouridine biogenesis at tRNA wobble positions. Nucleic Acids Res. 37:1335-1352. http ://dx .doi .org /10 .1093 /nar /gkn1023
51. Oskarsson, T., E. Batlle, and J. Massagué. 2014. Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell. 14:306-321. http ://dx .doi .org /10 .1016 /j .stem .2014 .02 .002
52. Otero, G., J. Fellows, Y. Li, T. de Bizemont, A.M. Dirac, C.M. Gustafsson, H' Erdjument-Bromage, P. Tempst, and J.Q. Svejstrup. 1999. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol. Cell. 3:109-118. http ://dx .doi .org /10 .1016 /S1097 -2765(00)80179 -3
53. Pavon-Eternod, M., S. Gomes, R. Geslain, Q. Dai, M.R. Rosner, and T' Pan. 2009. tRNA over-expression in breast cancer and functional consequences. Nucleic Acids Res. 37:7268-7280. http ://dx .doi .org /10 .1093 /nar /gkp787
54. Petz, M., N. Them, H. Huber, H. Beug, and W. Mikulits. 2012. La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition. Nucleic Acids Res. 40:290-302. http ://dx .doi .org /10 .1093 /nar /gkr717
55. Privette Vinnedge, L.M., R. McClaine, P.K. Wagh, K.A. Wikenheiser- Brokamp, S.E. Waltz, and S.I. Wells. 2011. The human DEK oncogene stimulates ß-catenin signaling, invasion and mammosphere formation in breast cancer. Oncogene. 30:2741-2752. http ://dx .doi .org /10 .1038 /onc .2011 .2
56. Privette Vinnedge, L.M., N.M. Benight, and P.K. Wagh. 2014. The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers. Oncogene. 34:2325- 2536. http ://dx .doi .org /10 .1038 /onc .2014 .173
57. Pylayeva, Y., K.M. Gillen, W. Gerald, H.E. Beggs, L.F. Reichardt, and F.G' Giancotti. 2009. Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J. Clin. Invest' 119:252-266. http ://dx .doi .org /10 .1172 /JCI37160
58. Raptis, L., R. Marcellus, M.J. Corbley, A. Krook, J. Whitfield, S.K. Anderson, and T. Haliotis. 1991. Cellular ras gene activity is required for full neoplastic transformation by polyomavirus. J. Virol. 65:5203-5210'
59. Rezgui, V.A.N., K. Tyagi, N. Ranjan, A.L. Konevega, J. Mittelstaet, M.V' Rodnina, M. Peter, and P.G. Pedrioli. 2013. tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding. Proc. Natl. Acad. Sci. USA' 110:12289-12294. http ://dx .doi .org /10 .1073 /pnas .1300781110
60. Ringnér, M., E. Fredlund, J. Häkkinen, A. Borg, and J. Staaf. 2011. GOBO: gene expression-based outcome for breast cancer online. PLoS One' 6:e17911. http ://dx .doi .org /10 .1371 /journal .pone .0017911
61. Schlieker, C.D., A.G. Van der Veen, J.R. Damon, E. Spooner, and H.L. Ploegh' 2008. A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proc. Natl. Acad. Sci' USA. 105:18255-18260. http ://dx .doi .org /10 .1073 /pnas .0808756105
62. Schmidt, M., D. Böhm, C. von Törne, E. Steiner, A. Puhl, H. Pilch, H.A' Lehr, J.G. Hengstler, H. Kölbl, and M. Gehrmann. 2008. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 68:5405-5413. http ://dx .doi .org /10 .1158 /0008 -5472 .CAN -07 -5206
63. Selvadurai, K., P. Wang, J. Seimetz, and R.H. Huang. 2014. Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism. Nat. Chem. Biol. 10:810-812. http ://dx .doi .org /10 .1038 / nchembio .1610
64. Shibata, T., A. Kokubu, M. Miyamoto, F. Hosoda, M. Gotoh, K. Tsuta, H' Asamura, Y. Matsuno, T. Kondo, I. Imoto, et al. 2010. DEK oncoprotein regulates transcriptional modifiers and sustains tumor initiation activity in high-grade neuroendocrine carcinoma of the lung. Oncogene' 29:4671-4681. http ://dx .doi .org /10 .1038 /onc .2010 .217
65. Silvera, D., S.C. Formenti, and R.J. Schneider. 2010. Translational control in cancer. Nat. Rev. Cancer. 10:254-266. http ://dx .doi .org /10 .1038 / nrc2824
66. Soares, L.M.M., K. Zanier, C. Mackereth, M. Sattler, and J. Valcárcel. 2006' Intron removal requires proofreading of U2AF/3' splice site recognition by DEK. Science. 312:1961-1965. http ://dx .doi .org /10 .1126 /science .1128659
67. Songe-Møller, L., E. van den Born, V. Leihne, C.B. Vågbø, T. Kristoffersen, H.E' Krokan, F. Kirpekar, P.Ø. Falnes, and A. Klungland. 2010. Mammalian ALK BH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol. Cell. Biol. 30:1814-1827. http ://dx .doi .org /10 .1128 /MCB .01602 -09
68. Sotiriou, C., P. Wirapati, S. Loi, A. Harris, S. Fox, J. Smeds, H. Nordgren, P' Farmer, V. Praz, B. Haibe-Kains, et al. 2006. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J. Natl. Cancer Inst. 98:262-272. http ://dx .doi .org /10 .1093 /jnci /djj052
69. Taddei, M.L., E. Giannoni, G. Comito, and P. Chiarugi. 2013' Microenvironment and tumor cell plasticity: an easy way out. Cancer Lett. 341:80-96. http ://dx .doi .org /10 .1016 /j .canlet .2013 .01 .042
70. Tsai, B.P., X. Wang, L. Huang, and M.L. Waterman. 2011. Quantitative profiling of in vivo-assembled RNA-protein complexes using a novel integrated proteomic approach. Mol. Cell. Proteomics. 10:007385. http :// dx .doi .org /10 .1074 /mcp .M110 .007385
71. Tsai, B.P., J. Jimenez, S. Lim, K.D. Fitzgerald, M. Zhang, C.T.H. Chuah, H' Axelrod, L. Wilson, S.T. Ong, B.L. Semler, and M.L. Waterman. 2014. A novel Bcr-Abl-mTOR-eIF4A axis regulates IRES-mediated translation of LEF-1. Open Biol. 4:140180. http ://dx .doi .org /10 .1098 /rsob .140180
72. Valastyan, S., and R.A. Weinberg. 2011. Tumor metastasis: molecular insights and evolving paradigms. Cell. 147:275-292. http ://dx .doi .org /10 .1016 /j .cell .2011 .09 .024
73. Waldmeier, L., N. Meyer-Schaller, M. Diepenbruck, and G. Christofori. 2012' Py2T murine breast cancer cells, a versatile model of TGFß-induced EMT in vitro and in vivo. PLoS One. 7:e48651. http ://dx .doi .org /10 .1371 /journal .pone .0048651
74. Wang, W.J., Y. Yao, L.L. Jiang, T.H. Hu, J.Q. Ma, Z.J. Liao, J.T. Yao, D.F. Li, S.H' Wang, and K.J. Nan. 2013. Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in vitro and in vivo. PLoS One' 8:e76596. http ://dx .doi .org /10 .1371 /journal .pone .0076596
75. Webster, M.A., J.N. Hutchinson, M.J. Rauh, S.K. Muthuswamy, M. Anton, C.G. Tortorice, R.D. Cardiff, F.L. Graham, J.A. Hassell, and W.J. Muller' 1998. Requirement for both Shc and phosphatidylinositol 3' kinase signaling pathways in polyomavirus middle T-mediated mammary tumorigenesis. Mol. Cell. Biol. 18:2344-2359. http ://dx .doi .org /10 .1128 /MCB .18 .4 .2344
76. Wise-Draper, T.M., R.A. Mintz-Cole, T.A. Morris, D.S. Simpson, K.A' Wikenheiser-Brokamp, M.A. Currier, T.P. Cripe, G.C. Grosveld, and S.I. Wells. 2009. Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo. Cancer Res. 69:1792-1799' http ://dx .doi .org /10 .1158 /0008 -5472 .CAN -08 -2304
77. Ye, X., W.L. Tam, T. Shibue, Y. Kaygusuz, F. Reinhardt, E. Ng Eaton, and R.A' Weinberg. 2015. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 525:256-260. http ://dx .doi .org /10 .1038 /nature14897
78. Zinshteyn, B., and W.V. Gilbert. 2013. Loss of a conserved tRNA anticodon modification perturbs cellular signaling. PLoS Genet. 9:e1003675. http ://dx .doi .org /10 .1371 /journal .pgen .1003675