Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3

Oncogene volume 34, pages 2032–2042 (2015)Cite this article

Subjects

Abstract

The progression of cancers from primary tumors to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Understanding the molecular events which promote metastasis is thus critical in the clinic. Translational control is emerging as an important factor in tumorigenesis. The messenger RNA (mRNA) cap-binding protein eIF4E is an oncoprotein that has an important role in cancer initiation and progression. eIF4E must be phosphorylated to promote tumor development. However, the role of eIF4E phosphorylation in metastasis is not known. Here, we show that mice in which eukaryotic translation initiation factor 4E (eIF4E) cannot be phosphorylated are resistant to lung metastases in a mammary tumor model, and that cells isolated from these mice exhibit impaired invasion. We also demonstrate that transforming growth factor-beta (TGFβ) induces eIF4E phosphorylation to promote the translation of Snail and Mmp-3 mRNAs, and the induction of epithelial-to-mesenchymal transition (EMT). Furthermore, we describe a new model wherein EMT induced by TGFβ requires translational activation via the non-canonical TGFβ signaling branch acting through eIF4E phosphorylation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Sonenberg N, Hinnebusch AG . Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 2009; 136: 731–745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hiremath LS, Webb NR, Rhoads RE . Immunological detection of the messenger RNA cap-binding protein. J Biol Chem 1985; 260: 7843–7849.

    CAS  PubMed  Google Scholar 

  3. Duncan R, Milburn SC, Hershey JW . Regulated phosphorylation and low abundance of HeLa cell initiation factor eIF-4F suggest a role in translational control. Heat shock effects on eIF-4F. J Biol Chem 1987; 262: 380–388.

    CAS  PubMed  Google Scholar 

  4. Pause A, Belsham GJ, Gingras AC, Donze O, Lin TA, Lawrence JC Jr. et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature 1994; 371: 762–767.

    Article  CAS  PubMed  Google Scholar 

  5. Poulin F, Gingras AC, Olsen H, Chevalier S, Sonenberg N . 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family. J Biol Chem 1998; 273: 14002–14007.

    Article  CAS  PubMed  Google Scholar 

  6. Flynn A, Proud CG . Serine 209, not serine 53, is the major site of phosphorylation in initiation factor eIF-4E in serum-treated Chinese hamster ovary cells. J Biol Chem 1995; 270: 21684–21688.

    Article  CAS  PubMed  Google Scholar 

  7. Joshi B, Cai AL, Keiper BD, Minich WB, Mendez R, Beach CM et al. Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. J Biol Chem 1995; 270: 14597–14603.

    Article  CAS  PubMed  Google Scholar 

  8. Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA . Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol 1999; 19: 1871–1880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N . Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J 1999; 18: 270–297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lazaris-Karatzas A, Montine KS, Sonenberg N . Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Nature 1990; 345: 544–547.

    Article  CAS  PubMed  Google Scholar 

  11. Ruggero D, Montanaro L, Ma L, Xu W, Londei P, Cordon-Cardo C et al. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med 2004; 10: 484–486.

    Article  CAS  PubMed  Google Scholar 

  12. Wendel HG, Silva RL, Malina A, Mills JR, Zhu H, Ueda T et al. Dissecting eIF4E action in tumorigenesis. Genes Dev 2007; 21: 3232–3237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mamane Y, Petroulakis E, Rong L, Yoshida K, Ler LW, Sonenberg N . eIF4E—from translation to transformation. Oncogene 2004; 23: 3172–3179.

    Article  CAS  PubMed  Google Scholar 

  14. Lee T, Pelletier J Eukaryotic initiation factor 4F: a vulnerability of tumor cells. Future Med Chem 2012; 4: 19–31.

    Article  CAS  PubMed  Google Scholar 

  15. Jia Y, Polunovsky V, Bitterman PB, Wagner CR . Cap-dependent translation initiation factor eIF4E: an emerging anticancer drug target. Med Res Rev 2012; 32: 786–814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Malina A, Mills JR, Pelletier J . Emerging therapeutics targeting mRNA translation. Cold Spring Harb Perspect Biol 2012; 4: a012377.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Topisirovic I, Ruiz-Gutierrez M, Borden KL . Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities. Cancer Res 2004; 64: 8639–8642.

    Article  CAS  PubMed  Google Scholar 

  18. Ueda T, Sasaki M, Elia AJ, Chio II, Hamada K, Fukunaga R et al. Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development. Proc Natl Acad Sci USA 2010; 107: 13984–13990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Konicek BW, Stephens JR, McNulty AM, Robichaud N, Peery RB, Dumstorf CA et al. Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases. Cancer Res 2011; 71: 1849–1857.

    Article  CAS  PubMed  Google Scholar 

  20. De Benedetti A, Graff JR . eIF-4E expression and its role in malignancies and metastases. Oncogene 2004; 23: 3189–3199.

    Article  CAS  PubMed  Google Scholar 

  21. Nasr Z, Robert F, Porco JA, Muller WJ, Pelletier J . eIF4F suppression in breast cancer affects maintenance and progression. Oncogene 2012; 32: 861–871.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pettersson F, Yau C, Dobocan MC, Culjkovic-Kraljacic B, Retrouvey H, Puckett R et al. Ribavirin treatment effects on breast cancers overexpressing eIF4E, a biomarker with prognostic specificity for luminal B-type breast cancer. Clin Cancer Res 2011; 17: 2874–2884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Graff JR, Konicek BW, Lynch RL, Dumstorf CA, Dowless MS, McNulty AM et al. eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival. Cancer Res 2009; 69: 3866–3873.

    Article  CAS  PubMed  Google Scholar 

  24. Furic L, Rong L, Larsson O, Koumakpayi IH, Yoshida K, Brueschke A et al. eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. Proc Natl Acad Sci USA 2010; 107: 14134–14139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li L, Price JE, Fan D, Zhang RD, Bucana CD, Fidler IJ . Correlation of growth capacity of human tumor cells in hard agarose with their in vivo proliferative capacity at specific metastatic sites. J Natl Cancer Inst 1989; 81: 1406–1412.

    Article  CAS  PubMed  Google Scholar 

  26. Friedl P, Alexander S . Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 2011; 147: 992–1009.

    Article  CAS  PubMed  Google Scholar 

  27. Lochter A, Galosy S, Muschler J, Freedman N, Werb Z, Bissell MJ . Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J Cell Biol 1997; 139: 1861–1872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. DaSilva J, Xu L, Kim HJ, Miller WT, Bar-Sagi D . Regulation of sprouty stability by Mnk1-dependent phosphorylation. Mol Cell Biol 2006; 26: 1898–1907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hefner Y, Borsch-Haubold AG, Murakami M, Wilde JI, Pasquet S, Schieltz D et al. Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J Biol Chem 2000; 275: 37542–37551.

    Article  CAS  PubMed  Google Scholar 

  30. Guil S, Long JC, Caceres JF . hnRNPA1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol 2006; 26: 5744–5758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Buxade M, Parra JL, Rousseau S, Shpiro N, Marquez R, Morrice N et al. The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNPA1. Immunity 2005; 23: 177–189.

    Article  CAS  PubMed  Google Scholar 

  32. Byers HR, Etoh T, Doherty JR, Sober AJ, Mihm MC Jr. . Cell migration and actin organization in cultured human primary, recurrent cutaneous and metastatic melanoma. Time-lapse and image analysis. Am J Pathol 1991; 139: 423–435.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987; 47: 3239–3245.

    CAS  PubMed  Google Scholar 

  34. Sommers CL, Byers SW, Thompson EW, Torri JA, Gelmann EP . Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Treat 1994; 31: 325–335.

    Article  CAS  PubMed  Google Scholar 

  35. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature 2012; 485: 55–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Huang da W, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44–57.

    Article  PubMed  Google Scholar 

  37. Huang da W, Sherman BT, Lempicki RA . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37: 1–13.

    Article  PubMed  Google Scholar 

  38. Kalluri R, Weinberg RA . The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119: 1420–1428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xu J, Lamouille S, Derynck R . TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009; 19: 156–172.

    Article  CAS  PubMed  Google Scholar 

  40. Zeisberg M, Neilson EG . Biomarkers for epithelial-mesenchymal transitions. J Clin Invest 2009; 119: 1429–1437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang YE . Non-Smad pathways in TGF-beta signaling. Cell Res 2009; 19: 128–139.

    Article  CAS  PubMed  Google Scholar 

  42. Bakin AV, Rinehart C, Tomlinson AK, Arteaga CL . p38 mitogen-activated protein kinase is required for TGFbeta-mediated fibroblastic transdifferentiation and cell migration. J Cell Sci 2002; 115: 3193–3206.

    CAS  PubMed  Google Scholar 

  43. Inman GJ, Nicolas FJ, Callahan JF, Harling JD, Gaster LM, Reith AD et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 2002; 62: 65–74.

    Article  CAS  PubMed  Google Scholar 

  44. Imamura T, Hikita A, Inoue Y . The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis. Breast Cancer 2012; 19: 118–124.

    Article  PubMed  Google Scholar 

  45. Knauf U, Tschopp C, Gram H . Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol Cell Biol 2001; 21: 5500–5511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Scheper GC, Morrice NA, Kleijn M, Proud CG . The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol 2001; 21: 743–754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Aslakson CJ, Miller FR . Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res 1992; 52: 1399–1405.

    CAS  PubMed  Google Scholar 

  48. Guy CT, Cardiff RD, Muller WJ . Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 1992; 12: 954–961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dilworth SM . Polyoma virus middle T antigen and its role in identifying cancer-related molecules. Nat Rev Cancer 2002; 2: 951–956.

    Article  CAS  PubMed  Google Scholar 

  50. Franci C, Takkunen M, Dave N, Alameda F, Gomez S, Rodriguez R et al. Expression of Snail protein in tumor-stroma interface. Oncogene 2006; 25: 5134–5144.

    Article  CAS  PubMed  Google Scholar 

  51. Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH . Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 1996; 149: 273–282.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Li BD, McDonald JC, Nassar R, De Benedetti A . Clinical outcome in stage I to III breast carcinoma and eIF4E overexpression. Ann Surg 1998; 227: 756–6l discussion 61-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li BD, Gruner JS, Abreo F, Johnson LW, Yu H, Nawas S et al. Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome. Ann Surg 2002; 235: 732–738 discussion 8–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Holm N, Byrnes K, Johnson L, Abreo F, Sehon K, Alley J et al. A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-negative breast cancer. Ann Surg Oncol 2008; 15: 3207–3215.

    Article  PubMed  Google Scholar 

  55. McClusky DR, Chu Q, Yu H, Debenedetti A, Johnson LW, Meschonat C et al. A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-positive breast cancer. Ann Surg 2005; 242: 584–590 discussion 90-2.

    PubMed  PubMed Central  Google Scholar 

  56. Crew JP, Fuggle S, Bicknell R, Cranston DW, de Benedetti A, Harris AL . Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression. Br J Cancer 2000; 82: 161–166.

    Article  CAS  PubMed  Google Scholar 

  57. Seki N, Takasu T, Mandai K, Nakata M, Saeki H, Heike Y et al. Expression of eukaryotic initiation factor 4E in atypical adenomatous hyperplasia and adenocarcinoma of the human peripheral lung. Clin Cancer Res 2002; 8: 3046–3053.

    CAS  PubMed  Google Scholar 

  58. Seki N, Takasu T, Sawada S, Nakata M, Nishimura R, Segawa Y et al. Prognostic significance of expression of eukaryotic initiation factor 4E and 4E binding protein 1 in patients with pathological stage I invasive lung adenocarcinoma. Lung Cancer 2010; 70: 329–334.

    Article  PubMed  Google Scholar 

  59. Nathan CO, Franklin S, Abreo FW, Nassar R, De Benedetti A, Glass J . Analysis of surgical margins with the molecular marker eIF4E: a prognostic factor in patients with head and neck cancer. J Clin Oncol 1999; 17: 2909–2914.

    Article  CAS  PubMed  Google Scholar 

  60. Wu M, Liu Y, Di X, Kang H, Zeng H, Zhao Y et al. EIF4E over-expresses and enhances cell proliferation and cell cycle progression in nasopharyngeal carcinoma. Med Oncol 2013; 30: 400.

    Article  PubMed  Google Scholar 

  61. Wang XL, Cai HP, Ge JH, Su XF . Detection of eukaryotic translation initiation factor 4E and its clinical significance in hepatocellular carcinoma. World J Gastroenterol 2012; 18: 2540–2544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Salehi Z, Mashayekhi F . Expression of the eukaryotic translation initiation factor 4E (eIF4E) and 4E-BP1 in esophageal cancer. Clin Biochem 2006; 39: 404–409.

    Article  CAS  PubMed  Google Scholar 

  63. Chen CN, Hsieh FJ, Cheng YM, Lee PH, Chang KJ . Expression of eukaryotic initiation factor 4E in gastric adenocarcinoma and its association with clinical outcome. J Surg Oncol 2004; 86: 22–27.

    Article  CAS  PubMed  Google Scholar 

  64. Nathan CO, Carter P, Liu L, Li BD, Abreo F, Tudor A et al. Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas. Oncogene 1997; 15: 1087–1094.

    Article  CAS  PubMed  Google Scholar 

  65. Scott PA, Smith K, Poulsom R, De Benedetti A, Bicknell R, Harris AL . Differential expression of vascular endothelial growth factor mRNA vs protein isoform expression in human breast cancer and relationship to eIF-4E. Br J Cancer 1998; 77: 2120–2128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Byrnes K, White S, Chu Q, Meschonat C, Yu H, Johnson LW et al. High eIF4E, VEGF, and microvessel density in stage I to III breast cancer. Ann Surg 2006; 243: 684–690.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Fan S, Ramalingam SS, Kauh J, Xu Z, Khuri FR, Sun SY . Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues. Cancer Biol Ther 2009; 8: 1463–1469.

    Article  PubMed  Google Scholar 

  68. Yoshizawa A, Fukuoka J, Shimizu S, Shilo K, Franks TJ, Hewitt SM et al. Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Clin Cancer Res 2010; 16: 240–248.

    Article  CAS  PubMed  Google Scholar 

  69. Zheng J, Li J, Xu L, Xie G, Wen Q, Luo J et al. Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma. PLoS ONE 2014; 9: e89220.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Ferrandiz-Pulido C, Masferrer E, Toll A, Hernandez-Losa J, Mojal S, Pujol RM et al. mTOR signaling pathway in penile squamous cell carcinoma: pmTOR and peIF4E over expression correlate with aggressive tumor behavior. J Urol 2013; 190: 2288–2295.

    Article  CAS  PubMed  Google Scholar 

  71. Adesso L, Calabretta S, Barbagallo F, Capurso G, Pilozzi E, Geremia R et al. Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway. Oncogene 2013; 32: 2848–2857.

    Article  CAS  PubMed  Google Scholar 

  72. Grzmil M, Morin P Jr, Lino MM, Merlo A, Frank S, Wang Y et al. MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-beta signaling pathway in human glioblastoma. Cancer Res 2011; 71: 2392–2402.

    Article  CAS  PubMed  Google Scholar 

  73. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005; 65: 7052–7058.

    Article  CAS  PubMed  Google Scholar 

  74. Yin B, Morgan K, Hasz DE, Mao Z, Largaespada DA . Nfl gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. Leukemia 2006; 20: 151–154.

    Article  CAS  PubMed  Google Scholar 

  75. Astanehe A, Finkbeiner MR, Krzywinski M, Fotovati A, Dhillon J, Berquin IM et al. MKNK1 is a YB-1 target gene responsible for imparting trastuzumab resistance and can be blocked by RSK inhibition. Oncogene 2012; 31: 4434–4446.

    Article  CAS  PubMed  Google Scholar 

  76. Ramón y Cajal, Rojo S, Pone S, Castellana B, Hernandez Losa B, Sonenberg J et al. Clinical Translational Oncology (in press).

  77. C.S.H. Laboratory, RIPA buffer (05-01). Cold Spring Harbor Protocols, 2006. 2006(4): p. pdb.rec10617. http://cshprotocols.cshlp.org/content/2006/4/pdb.rec10617.short.

  78. Ling C, Su VM, Zuo D, Muller WJ . Loss of the 14-3-3sigma tumor suppressor is a critical event in ErbB2-mediated tumor progression. Cancer Discov 2012; 2: 68–81.

    Article  CAS  PubMed  Google Scholar 

  79. Alain T, Morita M, Fonseca BD, Yanagiya A, Siddiqui N, Bhat M et al. eIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies. Cancer Res 2012; 72: 6468–6476.

    Article  CAS  PubMed  Google Scholar 

  80. Larsson O, Sonenberg N, Nadon R . Anota: analysis of differential translation in genome-wide studies. Bioinformatics 2011; 27: 1440–1441.

    Article  CAS  PubMed  Google Scholar 

  81. Larsson O, Sonenberg N, Nadon R . Identification of differential translation in genome wide studies. Proc Natl Acad Sci USA 2010; 107: 21487–21492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Huang da W, Sherman BT, Zheng X, Yang J, Imamichi T, Stephens R et al. Extracting biological meaning from large gene lists with DAVID. Curr Protoc Bioinformatics 2009. Chapter 13: Unit 13.

Download references

Acknowledgements

This work was by supported by The Susan G. Komen Breast Cancer Foundation (IIR12224057), and the Canadian Cancer Society (2010-700377) to NS. WHM was supported by the Cancer Research Society (2012-17280). LF was supported by PCFA#YI-0310. NS is a Howard Hughes Medical Institute Senior International Scholar. WHM is a Chercheur National of Fonds de la Recherche en Santé du Quebec (FRSQ). NR was supported by scholarships from the Fonds de la Recherche en Santé du Québec (20874), the Canadian Institutes of Health Research (220151) and the Vanier Canada Graduate Scholarship (267839). OL is supported by the Swedish Research Council, the Swedish Cancer Society and the Wallenberg Academy Fellows Program. We thank I Topisirovic for advice; C Zakaria, A Sylvestre, S Perreault and C Lister for technical assistance, N Siddiqui for critical reading of the manuscript and S Ramón y Cajal (the Vall d’Hebron University Hospital, Barcelona, Spain) for his support and insights into tumor heterogeneity. We thank the Animal Facility and the Histology Facility at the Goodman Cancer Research Centre for mouse work and tissue processing.

Author information

Author notes

  1. N Robichaud and S V del Rincon: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada,

    N Robichaud, J Hearnden, W J Muller & N Sonenberg

  2. Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada,

    S V del Rincon, B Huor, L A Petruccelli, C Goncalves & W H Miller

  3. Department of Biochemistry, Microbiology and Immunology, Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada,

    T Alain

  4. Signal Transduction Program, Sanford–Burnham Medical Research Institute, La Jolla, CA, USA,

    S Grotegut & C H Spruck

  5. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia,

    L Furic

  6. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden,

    O Larsson

Authors
  1. N Robichaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S V del Rincon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Huor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Alain
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L A Petruccelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Hearnden
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Goncalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Grotegut
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C H Spruck
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L Furic
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. O Larsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. W J Muller
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. W H Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. N Sonenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to W H Miller or N Sonenberg.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Oncogene website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Robichaud, N., del Rincon, S., Huor, B. et al. Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3. Oncogene 34, 2032–2042 (2015). https://doi.org/10.1038/onc.2014.146

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2014.146

This article is cited by

Search

Advanced search

Quick links