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mTOR, translation initiation and cancer

Oncogene volume 25, pages 6416–6422 (2006)Cite this article

Abstract

Control of mRNA translation plays a fundamental role in many aspects of cell metabolism. It constitutes a critical step in the control of gene expression, and consequently cell growth, proliferation and differentiation. Translation is regulated in response to nutrient availability, hormones, mitogenic and growth factor stimulation and is coupled with cell cycle progression and cell growth. Signaling by the PI3K/Akt/mTOR pathway profoundly affects mRNA translation through phosphorylation of downstream targets such as 4E-BP and S6K. Inhibitors of this pathway and thus cap-dependent translation are emerging as promising therapeutic options for the treatment of cancer.

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References

  • Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman DM et al. (2004). Cancer Cell 5: 553–563.

  • Bauer C, Brass N, Diesinger I, Kayser K, Grasser FA, Meese E . (2002). Int J Cancer 98: 181–185.

  • Bauer C, Diesinger I, Brass N, Steinhart H, Iro H, Meese EU . (2001). Cancer 92: 822–829.

  • Brass N, Heckel D, Sahin U, Pfreundschuh M, Sybrecht GW, Meese E . (1997). Hum Mol Genet 6: 33–39.

  • Clemens MJ . (2001). J Cell Mol Med 5: 221–239.

  • De Virgilio C, Loewith R . (2006). Int J Biochem Cell Biol 38: 1476–1481.

  • Dilling MB, Germain GS, Dudkin L, Jayaraman AL, Zhang X, Harwood FC et al. (2002). J Biol Chem 277: 13907–13917.

  • Dua K, Williams TM, Beretta L . (2001). Proteomics 1: 1191–1199.

  • Duncan R, Milburn SC, Hershey JW . (1987). J Biol Chem 262: 380–388.

  • Eberle J, Krasagakis K, Orfanos CE . (1997). Int J Cancer 71: 396–401.

  • Edinger AL, Thompson CB . (2002). Mol Biol Cell 13: 2276–2288.

  • Fingar DC, Richardson CJ, Tee AR, Cheatham L, Tsou C, Blenis J . (2004). Mol Cell Biol 24: 200–216.

  • Fingar DC, Salama S, Tsou C, Harlow E, Blenis J . (2002). Genes Dev 16: 1472–1487.

  • Fukuchi-Shimogori T, Ishii I, Kashiwagi K, Mashiba H, Ekimoto H, Igarashi K . (1997). Cancer Res 57: 5041–5044.

  • Fukunaga R, Hunter T . (1997). EMBO J 16: 1921–1933.

  • Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF et al. (1999a). Genes Dev 13: 1422–1437.

  • Gingras AC, Raught B, Gygi SP, Niedzwiecka A, Miron M, Burley SK et al. (2001). Genes Dev 15: 2852–2864.

  • Gingras AC, Raught B, Sonenberg N . (1999b). Annu Rev Biochem 68: 913–963.

  • Grolleau A, Bowman J, Pradet-Balade B, Puravs E, Hanash S, Garcia-Sanz JA et al. (2002). J Biol Chem 277: 22175–22184.

  • Harris TE, Chi A, Shabanowitz J, Hunt DF, Rhoads RE, Lawrence Jr JC . (2006). EMBO J 25: 1659–1668.

  • Hay N, Sonenberg N . (2004). Genes Dev 18: 1926–1945.

  • Henis-Korenblit S, Shani G, Sines T, Marash L, Shohat G, Kimchi A . (2002). Proc Natl Acad Sci USA 99: 5400–5405.

  • Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB . (2005). Nat Rev Drug Discov 4: 988–1004.

  • Hiremath LS, Webb NR, Rhoads RE . (1985). J Biol Chem 260: 7843–7849.

  • Holz MK, Ballif BA, Gygi SP, Blenis J . (2005). Cell 123: 569–580.

  • Hu C, Pang S, Kong X, Velleca M, Lawrence Jr JC . (1994). Proc Natl Acad Sci USA 91: 3730–3734.

  • Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H et al. (2003). Mol Cell 11: 1491–1501.

  • Imataka H, Olsen HS, Sonenberg N . (1997). EMBO J 16: 817–825.

  • Jacinto E, Hall MN . (2003). Nat Rev Mol Cell Biol 4: 117–126.

  • Keiper BD, Gan W, Rhoads RE . (1999). Int J Biochem Cell Biol 31: 37–41.

  • Kim DH, Sabatini DM . (2004). Curr Top Microbiol Immunol 279: 259–270.

  • Kim DH, Sarbassov dos D, Ali SM, Latek RR, Guntur KV, Erdjument-Bromage H et al. (2003). Mol Cell 11: 895–904.

  • Lazaris-Karatzas A, Montine KS, Sonenberg N . (1990). Nature 345: 544–547.

  • Lazaris-Karatzas A, Sonenberg N . (1992). Mol Cell Biol 12: 1234–1238.

  • Li S, Perlman DM, Peterson MS, Burrichter D, Avdulov S, Polunovsky VA et al. (2004). J Biol Chem 279: 21312–21317.

  • Li S, Sonenberg N, Gingras AC, Peterson M, Avdulov S, Polunovsky VA et al. (2002). Mol Cell Biol 22: 2853–2861.

  • Li S, Takasu T, Perlman DM, Peterson MS, Burrichter D, Avdulov S et al. (2003). J Biol Chem 278: 3015–3022.

  • Lynch M, Fitzgerald C, Johnston KA, Wang S, Schmidt EV . (2004). J Biol Chem 279: 3327–3339.

  • Mamane Y, Petroulakis E, Rong L, Yoshida K, Ler LW, Sonenberg N . (2004). Oncogene 23: 3172–3179.

  • Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK . (1999). Mol Cell 3: 707–716.

  • Meyuhas O . (2000). Eur J Biochem 267: 6321–6330.

  • Mungamuri SK, Yang X, Thor AD, Somasundaram K . (2006). Cancer Res 66: 4715–4724.

  • Okamoto H, Yasui K, Zhao C, Arii S, Inazawa J . (2003). Hepatology 38: 1242–1249.

  • Oridate N, Kim HJ, Xu X, Lotan R . (2005). Cancer Biol Ther 4: 318–323.

  • Paley PJ, Staskus KA, Gebhard K, Mohanraj D, Twiggs LB, Carson LF et al. (1997). Cancer 80: 98–106.

  • Panner A, James CD, Berger MS, Pieper RO . (2005). Mol Cell Biol 25: 8809–8823.

  • Panner A, Parsa AT, Pieper RO . (2006). Cell Cycle 5: 147–150.

  • Pause A, Belsham GJ, Gingras AC, Donze O, Lin TA, Lawrence Jr JC et al. (1994). Nature 371: 762–767.

  • Pende M, Um SH, Mieulet V, Sticker M, Goss VL, Mestan J et al. (2004). Mol Cell Biol 24: 3112–3124.

  • Peterson TR, Sabatini DM . (2005). Mol Cell 20: 655–657.

  • Petroulakis E, Mamane Y, Le Bacquer O, Shahbazian D, Sonenberg N . (2006). Br J Cancer 94: 195–199.

  • Polunovsky VA, Gingras AC, Sonenberg N, Peterson M, Tan A, Rubins JB et al. (2000). J Biol Chem 275: 24776–24780.

  • Polunovsky VA, Rosenwald IB, Tan AT, White J, Chiang L, Sonenberg N et al. (1996). Mol Cell Biol 16: 6573–6581.

  • Poulin F, Gingras AC, Olsen H, Chevalier S, Sonenberg N . (1998). J Biol Chem 273: 14002–14007.

  • Proud CG . (2004). Curr Top Microbiol Immunol 279: 215–244.

  • Proud CG . (2005). Cell Death Differ 12: 541–546.

  • Raught B, Gingras AC, Gygi SP, Imataka H, Morino S, Gradi A et al. (2000). EMBO J 19: 434–444.

  • Rousseau D, Gingras AC, Pause A, Sonenberg N . (1996). Oncogene 13: 2415–2420.

  • Rowinsky EK . (2004). Curr Opin Oncol 16: 564–575.

  • Ruggero D, Montanaro L, Ma L, Xu W, Londei P, Cordon-Cardo C et al. (2004). Nat Med 10: 484–486.

  • Ruggero D, Pandolfi PP . (2003). Nat Rev Cancer 3: 179–192.

  • Savinainen KJ, Linja MJ, Saramaki OR, Tammela TL, Chang GT, Brinkmann AO et al. (2004). Br J Cancer 90: 1041–1046.

  • Schmalfeldt B, Prechtel D, Harting K, Spathe K, Rutke S, Konik E et al. (2001). Clin Cancer Res 7: 2396–2404.

  • Schmidt EV . (2004). Oncogene 23: 3217–3221.

  • Shahbazian D, Roux PP, Mieulet V, Cohen MS, Raught B, Taunton J et al. (2006). EMBO J 25: 2781–2791.

  • Shi J, Kahle A, Hershey JW, Honchak BM, Warneke JA, Leong SP et al. (2006). Oncogene doi:10.1038/sj.onc.1209495.

  • Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma SC . (1998). EMBO J 17: 6649–6659.

  • Shuda M, Kondoh N, Tanaka K, Ryo A, Wakatsuki T, Hada A et al. (2000). Anticancer Res 20: 2489–2494.

  • Skinner HD, Zheng JZ, Fang J, Agani F, Jiang BH . (2004). J Biol Chem 279: 45643–45651.

  • Stephens L, Williams R, Hawkins P . (2005). Curr Opin Pharmacol 5: 357–365.

  • Stolovich M, Tang H, Hornstein E, Levy G, Cohen R, Bae SS et al. (2002). Mol Cell Biol 22: 8101–8113.

  • Tan A, Bitterman P, Sonenberg N, Peterson M, Polunovsky V . (2000). Oncogene 19: 1437–1447.

  • Tang H, Hornstein E, Stolovich M, Levy G, Livingstone M, Templeton D et al. (2001). Mol Cell Biol 21: 8671–8683.

  • Tee AR, Proud CG . (2002). Mol Cell Biol 22: 1674–1683.

  • Thomas GV . (2006). Curr Opin Genet Dev 16: 78–84.

  • Topisirovic I, Ruiz-Gutierrez M, Borden KL . (2004). Cancer Res 64: 8639–8642.

  • Wang FQ, So J, Reierstad S, Fishman DA . (2006). Int J Cancer 118: 879–888.

  • Wang S, El-Deiry WS . (2003). Oncogene 22: 8628–8633.

  • Warnakulasuriyarachchi D, Cerquozzi S, Cheung HH, Holcik M . (2004). J Biol Chem 279: 17148–17157.

  • Waskiewicz AJ, Flynn A, Proud CG, Cooper JA . (1997). EMBO J 16: 1909–1920.

  • Wendel HG, De Stanchina E, Fridman JS, Malina A, Ray S, Kogan S et al. (2004). Nature 428: 332–337.

  • Yamanaka S, Poksay KS, Arnold KS, Innerarity TL . (1997). Genes Dev 11: 321–333.

  • Yan H, Frost P, Shi Y, Hoang B, Sharma S, Fisher M et al. (2006). Cancer Res 66: 2305–2313.

  • Young DA, Nickerson-Nutter CL . (2005). Curr Opin Pharmacol 5: 418–423.

  • Zhou HY, Wong AS . (2006). Endocrinology 147: 2557–2566.

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Acknowledgements

We thank C Lister and P Kirk for their assistance. This research was supported by grants from the National Cancer Institute of Canada (NCIC), Canadian Institute of Health Research (CIHR) and the Howard Hughes Medical Institute (HHMI). YM is a recipient of a fellowship from the NCIC. EP was supported by a Fellowship from the Cancer Research Society and a Chemical Biology Fellowship from McGill University. OL is a recipient of a Chemical Biology Fellowship from McGill University. NS is a CIHR distinguished scientist and an HHMI International Scholar.

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

    Y Mamane, E Petroulakis, O LeBacquer & N Sonenberg

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Correspondence to N Sonenberg.

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Mamane, Y., Petroulakis, E., LeBacquer, O. et al. mTOR, translation initiation and cancer. Oncogene 25, 6416–6422 (2006). https://doi.org/10.1038/sj.onc.1209888

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