Adaptation to mTOR kinase inhibitors by amplification of eIF4E to maintain cap-dependent translation

Journal of Cell Science

Volumn 127, Issue 4, 2014, Pages 788-800

  Cope, Claire L ^a   Gilley, Rebecca ^a   Balmanno, Kathryn ^a   Sale, Matthew J ^a   Howarth, Karen D ^b   Hampson, Mark ^c   Smith, Paul D ^c   Guichard, Sylvie M ^c   Cook, Simon J ^a  

^a BABRAHAM INSTITUTE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c ASTRAZENECA   (United Kingdom)

Author keywords

4EBP1; Cell proliferation; Drug resistance; EIF4E; Gene amplification; MTOR

Indexed keywords

4EBP1; CELL PROLIFERATION; DRUG RESISTANCE; EIF4E; GENE AMPLIFICATION; MTOR;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; EUKARYOTIC INITIATION FACTOR-4E; G1 PHASE CELL CYCLE CHECKPOINTS; GENE AMPLIFICATION; HUMANS; MORPHOLINES; PHOSPHOPROTEINS; PROTEIN BIOSYNTHESIS; RIBOSOMAL PROTEIN S6 KINASES; RNA, MESSENGER; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84894095058     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.137588     Document Type: Article

References (59)

1. Alain, T., Morita, M., Fonseca, B. D., Yanagiya, A., Siddiqui, N., Bhat, M., Zammit, D., Marcus, V., Metrakos, P., Voyer, L. A. et al. (2012). eIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies. Cancer Res. 72, 6468-6476.
2. Alsop, A. E., Teschendorff, A. E. and Edwards, P. A. (2006). Distribution of breakpoints on chromosome 18 in breast, colorectal, and pancreatic carcinoma cell lines. Cancer Genet. Cytogenet. 164, 97-109.
3. Averous, J., Fonseca, B. D. and Proud, C. G. (2008). Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene 27, 1106-1113.
4. Benjamin, D., Colombi, M., Moroni, C. and Hall, M. N. (2011). Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat. Rev. Drug Discov. 10, 868-880.
5. Brunn, G. J., Hudson, C. C., Sekulić , A., Williams, J. M., Hosoi, H., Houghton, P. J., Lawrence, J. C., Jr and Abraham, R. T. (1997). Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science 277, 99-101.
6. Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M. et al.; BRIM-3 Study Group (2011). Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507-2516.
7. Choo, A. Y. and Blenis, J. (2009). Not all substrates are treated equally: implications for mTOR, rapamycin-resistance and cancer therapy. Cell Cycle 8, 567-572.
8. Choo, A. Y., Yoon, S. O., Kim, S. G., Roux, P. P. and Blenis, J. (2008). Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc. Natl. Acad. Sci. USA 105, 17414-17419.
9. Chresta, C. M., Davies, B. R., Hickson, I., Harding, T., Cosulich, S., Critchlow, S. E., Vincent, J. P., Ellston, R., Jones, D., Sini, P. et al. (2010). AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 70, 288-298.
10. Coleman, J. and Miskimins, W. K. (2009). Structure and activity of the internal ribosome entry site within the human p27 Kip1 59-untranslated region. RNA Biol. 6, 84-89.
11. Culjkovic, B., Topisirovic, I., Skrabanek, L., Ruiz-Gutierrez, M. and Borden, K. L. (2005). eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 39UTR. J. Cell Biol. 169, 245-256.
12. Davies, B. R., Logie, A., McKay, J. S., Martin, P., Steele, S., Jenkins, R., Cockerill, M., Cartlidge, S. and Smith, P. D. (2007). AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases:mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 6, 2209-2219.
13. De Benedetti, A. and Graff, J. R. (2004). eIF-4E expression and its role in malignancies and metastases. Oncogene 23, 3189-3199.
14. Dennis, M. D., Kimball, S. R. and Jefferson, L. S. (2013). Mechanistic target of rapamycin complex 1 (mTORC1)-mediated phosphorylation is governed by competition between substrates for interaction with raptor. J. Biol. Chem. 288, 10-19.
15. Dowling, R. J., Topisirovic, I., Alain, T., Bidinosti, M., Fonseca, B. D., Petroulakis, E., Wang, X., Larsson, O., Selvaraj, A., Liu, Y. et al. (2010). mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4EBPs. Science 328, 1172-1176.
16. Elia, A., Constantinou, C. and Clemens, M. J. (2008). Effects of protein phosphorylation on ubiquitination and stability of the translational inhibitor protein 4E-BP1. Oncogene 27, 811-822.
17. Feldman, M. E., Apsel, B., Uotila, A., Loewith, R., Knight, Z. A., Ruggero, D. and Shokat, K. M. (2009). Active-site inhibitors of mTOR target rapamycinresistant outputs of mTORC1 and mTORC2. PLoS Biol. 7, e38.
18. Furic, L., Rong, L., Larsson, O., Koumakpayi, I. H., Yoshida, K., Brueschke, A., Petroulakis, E., Robichaud, N., Pollak, M., Gaboury, L. A. et al. (2010). eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. Proc. Natl. Acad. Sci. USA 107, 14134-14139.
19. Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P. et al. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883-892.
20. Gingras, A. C., Kennedy, S. G., O'Leary, M. A., Sonenberg, N. and Hay, N. (1998). 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12, 502-513.
21. Harrington, L. S., Findlay, G. M., Gray, A., Tolkacheva, T., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N. R., Cheng, S., Shepherd, P. R. et al. (2004). The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166, 213-223.
22. Haydon, M. S., Googe, J. D., Sorrells, D. S., Ghali, G. E. and Li, B. D. (2000). Progression of eIF4e gene amplification and overexpression in benign and malignant tumors of the head and neck. Cancer 88, 2803-2810.
23. Holt, S. V., Logie, A., Davies, B. R., Alferez, D., Runswick, S., Fenton, S., Chresta, C. M., Gu, Y., Zhang, J., Wu, Y. L. et al. (2012). Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055). Cancer Res. 72, 1804-1813.
24. Hou, J., Lam, F., Proud, C. and Wang, S. (2012). Targeting Mnks for cancer therapy. Oncotarget. 3, 118-131.
25. Hsieh, A. C., Costa, M., Zollo, O., Davis, C., Feldman, M. E., Testa, J. R., Meyuhas, O., Shokat, K. M. and Ruggero, D. (2010). Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E. Cancer Cell 17, 249-261.
26. Hsu, P. P., Kang, S. A., Rameseder, J., Zhang, Y., Ottina, K. A., Lim, D., Peterson, T. R., Choi, Y., Gray, N. S., Yaffe, M. B. et al. (2011). The mTORregulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-1322.
27. Ilic, N., Utermark, T., Widlund, H. R. and Roberts, T. M. (2011). PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis. Proc. Natl. Acad. Sci. USA 108, E699-E708.
28. Jiang, H., Coleman, J., Miskimins, R., Srinivasan, R. and Miskimins, W. K. (2007). Cap-independent translation through the p27 59-UTR. Nucleic Acids Res. 35, 4767-4778.
29. Laplante, M. and Sabatini, D. M. (2012). mTOR signaling in growth control and disease. Cell 149, 274-293.
30. Lazaris-Karatzas, A., Montine, K. S. and Sonenberg, N. (1990). Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 59 cap. Nature 345, 544-547.
31. Li, S., Sonenberg, N., Gingras, A. C., Peterson, M., Avdulov, S., Polunovsky, V. A. and Bitterman, P. B. (2002). Translational control of cell fate: availability of phosphorylation sites on translational repressor 4E-BP1 governs its proapoptotic potency. Mol. Cell. Biol. 22, 2853-2861.
32. Little, A. S., Balmanno, K., Sale, M. J., Newman, S., Dry, J. R., Hampson, M., Edwards, P. A., Smith, P. D. and Cook, S. J. (2011). Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells. Sci. Signal. 4, ra17.
33. Little, A. S., Smith, P. D. and Cook, S. J. (2013). Mechanisms of acquired resistance to ERK1/2 pathway inhibitors. Oncogene 32, 1207-1215.
34. Mamane, Y., Petroulakis, E., Rong, L., Yoshida, K., Ler, L. W. and Sonenberg, N. (2004). eIF4E-from translation to transformation. Oncogene 23, 3172-3179.
35. Menon, S. and Manning, B. D. (2008). Common corruption of the mTOR signaling network in human tumors. Oncogene 27 Suppl. 2, S43-S51.
36. Pause, A., Belsham, G. J., Gingras, A. C., Donzé , O., Lin, T. A., Lawrence, J. C., Jr and Sonenberg, N. (1994). Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 59-cap function. Nature 371, 762-767.
37. Pole, J. C., Courtay-Cahen, C., Garcia, M. J., Blood, K. A., Cooke, S. L., Alsop, A. E., Tse, D. M., Caldas, C. and Edwards, P. A. (2006). High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation. Oncogene 25, 5693-5706.
38. Poulikakos, P. I., Zhang, C., Bollag, G., Shokat, K. M. and Rosen, N. (2010). RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wildtype BRAF. Nature 464, 427-430.
39. Rosenzweig, S. A. (2012). Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem. Pharmacol. 83, 1041-1048.
40. Ruggero, D., Montanaro, L., Ma, L., Xu, W., Londei, P., Cordon-Cardo, C. and Pandolfi, P. P. (2004). The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat. Med. 10, 484-486.
41. Sarbassov, D. D., Guertin, D. A., Ali, S. M. and Sabatini, D. M. (2005). Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101.
42. She, Q. B., Halilovic, E., Ye, Q., Zhen, W., Shirasawa, S., Sasazuki, T., Solit, D. B. and Rosen, N. (2010). 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 18, 39-51.
43. Shi, Y., Yan, H., Frost, P., Gera, J. and Lichtenstein, A. (2005). Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade. Mol. Cancer Ther. 4, 1533-1540.
44. Stoneley, M. and Willis, A. E. (2004). Cellular internal ribosome entry segments: structures, trans-acting factors and regulation of gene expression. Oncogene 23, 3200-3207.
45. Svitkin, Y. V., Herdy, B., Costa-Mattioli, M., Gingras, A. C., Raught, B. and Sonenberg, N. (2005). Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry sitemediated translation. Mol. Cell. Biol. 25, 10556-10565.
46. Tamburini, J., Chapuis, N., Bardet, V., Park, S., Sujobert, P., Willems, L., Ifrah, N., Dreyfus, F., Mayeux, P., Lacombe, C. et al. (2008). Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by upregulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways. Blood 111, 379-382.
47. Tan, A., Bitterman, P., Sonenberg, N., Peterson, M. and Polunovsky, V. (2000). Inhibition of Myc-dependent apoptosis by eukaryotic translation initiation factor 4E requires cyclin D1. Oncogene 19, 1437-1447.
48. Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M. and Gray, N. S. (2009). An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 284, 8023-8032.
49. Todd, D. E., Densham, R. M., Molton, S. A., Balmanno, K., Newson, C., Weston, C. R., Garner, A. P., Scott, L. and Cook, S. J. (2004). ERK1/2 and p38 cooperate to induce a p21CIP1-dependent G1 cell cycle arrest. Oncogene 23, 3284-3295.
50. Topisirovic, I., Ruiz-Gutierrez, M. and Borden, K. L. (2004). Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities. Cancer Res. 64, 8639-8642.
51. Tzatsos, A. and Kandror, K. V. (2006). Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol. Cell. Biol. 26, 63-76.
52. Ueda, T., Sasaki, M., Elia, A. J., Chio, I. I., Hamada, K., Fukunaga, R. and Mak, T. W. (2010). Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development. Proc. Natl. Acad. Sci. USA 107, 13984-13990.
53. Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J. et al. (2004). Absence of S6K1 protects against age-and diet-induced obesity while enhancing insulin sensitivity. Nature 431, 200-205.
54. Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A. and Speleman, F. (2002) Accurate normalization of real-time quantitative RTPCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, RESEARCH0034.
55. Waskiewicz, A. J., Flynn, A., Proud, C. G. and Cooper, J. A. (1997). Mitogenactivated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 16, 1909-1920.
56. Wendel, H. G., De Stanchina, E., Fridman, J. S., Malina, A., Ray, S., Kogan, S., Cordon-Cardo, C., Pelletier, J. and Lowe, S. W. (2004). Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 428, 332-337.
57. Wendel, H. G., Silva, R. L., Malina, A., Mills, J. R., Zhu, H., Ueda, T., Watanabe-Fukunaga, R., Fukunaga, R., Teruya-Feldstein, J., Pelletier, J. et al. (2007). Dissecting eIF4E action in tumorigenesis. Genes Dev. 21, 3232-3237.
58. Yu, Y., Yoon, S. O., Poulogiannis, G., Yang, Q., Ma, X. M., Villé n, J., Kubica, N., Hoffman, G. R., Cantley, L. C., Gygi, S. P. et al. (2011). Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-1326.
59. Zoncu, R., Efeyan, A. and Sabatini, D. M. (2011). mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12, 21-35.