Skip to main content Accessibility help
×
Home
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 1
  • Print publication year: 2015
  • Online publication date: April 2015

Chapter 6 - Regulation and dysregulation of protein synthesis in cancer cells

from Part 2 - Alterations in the regulatory networks of cellular and molecular events

Related content

Powered by UNSILO

References

Abbott, C.M. and Proud, C.G. (2004). Translation factors: in sickness and in health. Trends Biochem Sci 29, 25–31.
Andreopoulou, E. (2011). The PI3K/AKT/mTOR signaling pathway: implications in the treatment of breast cancer. Current Breast Cancer Rep 3, 63–74.
Andrieu, C., Taieb, D., Baylot, V., et al. (2010). Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E Oncogene 29, 1883–1896.
Aoki, M. and Vogt, P.K. (2004). Retroviral oncogenes and TOR. Curr Top Microbiol Immunol 279, 321–338.
Armengol, G., Rojo, F., Castellvi, J., et al. (2007). 4E-binding protein 1: a key molecular “funnel factor” in human cancer with clinical implications. Cancer Res 67, 7551–7555.
Asangani, I.A., Rasheed, S.A., Nikolova, D.A., et al. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27, 2128–2136.
Assouline, S., Culjkovic, B., Cocolakis, E., et al. (2009). Molecular targeting of the oncogene eIF4E in AML: a proof-of-principle clinical trial with ribavirin. Blood 114, 257–260.
Avdulov, S., Li, S., Michalek, V., et al. (2004). Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell 5, 553–563.
Balachandran, S. and Barber, G.N. (2004). Defective translational control facilitates vesicular stomatitis virus oncolysis. Cancer Cell 5, 51–65.
Balakumaran, B.S., Porrello, A., Hsu, D.S., et al. (2009). MYC activity mitigates response to rapamycin in prostate cancer through eukaryotic initiation factor 4E-binding protein 1-mediated inhibition of autophagy. Cancer Res 69, 7803–7810.
Barna, M., Pusic, A., Zollo, O., et al. (2008). Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature 456, 971–975.
Barnhart, B.C., Lam, J.C., Young, R.M., et al. (2008). Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell proliferation and survival. Cancer Biol Ther 7, 1441–1449.
Bauer, C., Brass, N., Diesinger, I., et al. (2002). Overexpression of the eukaryotic translation initiation factor 4G (eIF4G-1) in squamous cell lung carcinoma. Int J Cancer 98, 181–185.
Beuvink, I., Boulay, A., Fumagalli, S., et al. (2005). The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell 120, 747–759.
Bianchini, A., Loiarro, M., Bielli, P., et al. (2008). Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis 29, 2279–2288.
Bjornsti, M.A. and Houghton, P.J. (2004a). Lost in translation: dysregulation of cap-dependent translation and cancer. Cancer Cell 5, 519–523.
Bjornsti, M.A. and Houghton, P.J. (2004b). The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4, 335–348.
Blagden, S.P. and Willis, A.E. (2011). The biological and therapeutic relevance of mRNA translation in cancer. Nat Rev Clin Oncol 8, 280–591.
Blalock, W.L., Bavelloni, A., Piazzi, M., Faenza, I., and Cocco, L. (2010). A role for PKR in hematologic malignancies. J Cell Physiol 223, 572–591.
Blalock, W.L., Bavelloni, A., Piazzi, M., et al. (2011). Multiple forms of PKR present in the nuclei of acute leukemia cells represent an active kinase that is responsive to stress. Leukemia 25, 236–245.
Blazquez-Domingo, M., Grech, G., and von Lindern, M. (2005). Translation initiation factor 4E inhibits differentiation of erythroid progenitors. Mol Cell Biol 25, 8496–8506.
Braunstein, S., Karpisheva, K., Pola, C., et al. (2007). A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Mol Cell 28, 501–512.
Buxade, M., Parra-Palau, J.L., and Proud, C.G. (2008). The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Front Biosci 13, 5359–5373.
Carayol, N., Katsoulidis, E., Sassano, A., et al. (2008). Suppression of programmed cell death 4 (PDCD4) protein expression by BCR-ABL-regulated engagement of the mTOR/p70 S6 kinase pathway. J Biol Chem 283, 8601–8610.
Carraway, H. and Hidalgo, M. (2004). New targets for therapy in breast cancer: mammalian target of rapamycin (mTOR) antagonists. Breast Cancer Res 6, 219–224.
Carter, P.S., Jarquin-Pardo, M., and De Benedetti, A. (1999). Differential expression of Myc1 and Myc2 isoforms in cells transformed by eIF4E: evidence for internal ribosome repositioning in the human c-myc 5′UTR. Oncogene 18, 4326–4335.
Castellvi, J., Garcia, A., Rojo, F., et al. (2006). Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer. Cancer 107, 1801–1811.
Castellvi, J., Garcia, A., Ruiz-Marcellan, C., et al. (2009). Cell signaling in endometrial carcinoma: phosphorylated 4E-binding protein-1 expression in endometrial cancer correlates with aggressive tumors and prognosis. Hum Pathol 40, 1418–1426.
Cencic, R., Carrier, M., Trnkus, A., et al. (2010). Synergistic effect of inhibiting translation initiation in combination with cytotoxic agents in acute myelogenous leukemia cells. Leuk Res 34, 535–541.
Chan, S. (2004). Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer. Br J Cancer 91, 1420–1424.
Chang, J.H., Cho, Y.H., Sohn, S.Y., et al. (2009). Crystal structure of the eIF4A-PDCD4 complex. Proc Natl Acad Sci USA 106, 3148–3153.
Chappell, S.A., LeQuesne, J.P.C., Paulin, F.E.M., et al. (2000). A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene de-regulation. Oncogene 19, 4437–4440.
Chawla-Sarkar, M., Lindner, D.J., Liu, Y.F., et al. (2003). Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis 8, 237–249.
Chen, H., Ma, Z., Vanderwaal, R.P., et al. (2011). The mTOR inhibitor rapamycin suppresses DNA double-strand break repair. Radiat Res 175, 214–224.
Chen, Y., Liu, W., Chao, T., et al. (2008). MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G. Cancer Lett 272, 197–205.
Chendrimada, T.P., Finn, K.J., Ji, X., et al. (2007). MicroRNA silencing through RISC recruitment of eIF6. Nature 447, 823–828.
Cho, S., Kim, J.H., Back, S.H., and Jang, S.K. (2005). Polypyrimidine tract-binding protein enhances the internal ribosomal entry site-dependent translation of p27Kip1 mRNA and modulates transition from G1 to S phase. Mol Cell Biol 25, 1283–1297.
Choi, C.H., Lee, J.S., Kim, S.R., et al. (2011). Direct inhibition of eIF4E reduced cell growth in endometrial adenocarcinoma. J Cancer Res Clin Oncol 137, 463–469.
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.
Clemens, M.J. (2004). Targets and mechanisms for the regulation of translation in malignant transformation. Oncogene 23, 3180–3188.
Clemens, M.J. (2005). Translational control in virus-infected cells: models for cellular stress responses. Semin Cell Dev Biol 16, 13–20.
Coleman, L.J., Peter, M.B., Teall, T.J., et al. (2009). Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. Br J Cancer 100, 1393–1399.
Culjkovic, B., Tan, K., Orolicki, S., et al. (2008). The eIF4E RNA regulon promotes the Akt signaling pathway. J Cell Biol 181, 51–63.
Dancey, J. (2010). mTOR signaling and drug development in cancer. Nat Rev Clin Oncol 7, 209–219.
Dancey, J.E. (2003). mTOR inhibitors in hematologic malignancies. Clin Adv Hematol Oncol 1, 419–423.
De Benedetti, A. and Graff, J.R. (2004). eIF-4E expression and its role in malignancies and metastases. Oncogene 23, 3189–3199.
DeFatta, R.J., Chervenak, R.P., and De Benedetti, A. (2002a). A cancer gene therapy approach through translational control of a suicide gene. Cancer Gene Ther 9, 505–512.
DeFatta, R.J., Li, Y., and De Benedetti, A. (2002b). Selective killing of cancer cells based on translational control of a suicide gene. Cancer Gene Ther 9, 573–578.
Dong, K., Wang, R., Wang, X., et al. (2009). Tumor-specific RNAi targeting eIF4E suppresses tumor growth, induces apoptosis and enhances cisplatin cytotoxicity in human breast carcinoma cells. Breast Cancer Res Treat 113, 443–456.
Dong, Z., Liu, L.H., Han, B., Pincheira, R., and Zhang, J.T. (2004). Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth. Oncogene 23, 3790–3801.
Donze, O., Jagus, R., Koromilas, A.E., Hershey, J.W., and Sonenberg, N. (1995). Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells. EMBO J 14, 3828–3834.
Dorrello, N.V., Peschiaroli, A., Guardavaccaro, D., et al. (2006). S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 314, 467–471.
Dowling, R.J., Pollak, M., and Sonenberg, N. (2009). Current status and challenges associated with targeting mTOR for cancer therapy. BioDrugs 23, 77–91.
Dubois, L., Magagnin, M.G., Cleven, A.H., et al. (2009). Inhibition of 4E-BP1 sensitizes U87 glioblastoma xenograft tumors to irradiation by decreasing hypoxia tolerance. Int J Radiat Oncol Biol Phys 73, 1219–1227.
Dutcher, J.P. (2004). Mammalian target of rapamycin inhibition. Clin Cancer Res 10, 6382S–6387S.
Dutton, A., Reynolds, G.M., Dawson, C.W., Young, L.S., and Murray, P.G. (2005). Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the survival of Hodgkin's lymphoma cells through a mechanism involving Akt kinase and mTOR. J Pathol 205, 498–506.
Easton, J.B. and Houghton, P.J. (2004). Therapeutic potential of target of rapamycin inhibitors. Expert Opin Ther Targets 8, 551–564.
Eberle, J., Krasagakis, K., and Orfanos, C.E. (1997). Translation initiation factor eIF-4A1 mRNA is consistently overexpressed in human melanoma cells in vitro. Int J Cancer 71, 396–401.
Eberle, J., Fecker, L.F., Bittner, J.U., Orfanos, C.E., and Geilen, C.C. (2002). Decreased proliferation of human melanoma cell lines caused by antisense RNA against translation factor elF-4AI. Br J Cancer 86, 1957–1962.
Efeyan, A. and Sabatini, D.M. (2010). mTOR and cancer: many loops in one pathway. Curr Opin Cell Biol 22, 169–176.
Fan, S., Li, Y., Yue, P., Khuri, F.R., and Sun, S.Y. (2010). The eIF4E/eIF4G interaction inhibitor 4EGI-1 augments TRAIL-mediated apoptosis through c-FLIP down-regulation and DR5 induction independent of inhibition of cap-dependent protein translation. Neoplasia 12, 346–356.
Fan, S., Ramalingam, S.S., Kauh, J., et al. (2009). Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues. Cancer Biol Ther 8, 1463–1469.
Feldman, D.E., Chauhan, V., and Koong, A.C. (2005). The unfolded protein response: a novel component of the hypoxic stress response in tumors. Mol Cancer Res 3, 597–605.
Feng, P., Everly, D.N., Jr., and Read, G.S. (2005). mRNA decay during herpes simplex virus (HSV) infections: protein–protein interactions involving the HSV virion host shutoff protein and translation factors eIF4H and eIF4A. J Virol 79, 9651–9664.
Frederick, M.J., VanMeter, A.J., Gadhikar, M.A., et al. (2011). Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples. Am J Pathol 178, 548–571.
Fukuchi-Shimogori, T., Ishii, I., Kashiwagi, K., et al. (1997). Malignant transformation by overproduction of translation initiation factor eIF4G. Cancer Res 57, 5041–5044.
Furic, L., Livingstone, M., Dowling, R.J., and Sonenberg, N. (2009). Targeting mtor-dependent tumours with specific inhibitors: a model for personalized medicine based on molecular diagnoses. Curr Oncol 16, 59–61.
Gallagher, J.W., Kubica, N., Kimball, S.R., and Jefferson, L.S. (2008). Reduced eukaryotic initiation factor 2B epsilon-subunit expression suppresses the transformed phenotype of cells overexpressing the protein. Cancer Res 68, 8752–8760.
Gandin, V., Miluzio, A., Barbieri, A.M., et al. (2008). Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation. Nature 455, 684–688.
Garcia, M.A., Gil, J., Ventoso, I., et al. (2006). Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol Mol Biol Rev 70, 1032–1060.
Garcia-Maceira, P. and Mateo, J. (2009). Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene 28, 313–324.
Georgakis, G.V. and Younes, A. (2006). From Rapa Nui to rapamycin: targeting PI3K/Akt/mTOR for cancer therapy. Expert Rev Anticancer Ther 6, 131–140.
Gingras, A.C., Raught, B., and Sonenberg, N. (1999). eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem 68, 913–963.
Gomez-Martin, C., Rubio-Viqueira, B., and Hidalgo, M. (2005). Current status of mammalian target of rapamycin inhibitors in lung cancer. Clin Lung Cancer 7 Suppl 1, S13–S18.
Graff, J.R., Konicek, B.W., Carter, J.H., and Marcusson, E.G. (2008). Targeting the eukaryotic translation initiation factor 4E for cancer therapy. Cancer Res 68, 631–634.
Graff, J.R., Konicek, B.W., Lynch, R.L., et al. (2009). eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival. Cancer Res 69, 3866–3873.
Graff, J.R., Konicek, B.W., Vincent, T.M., et al. (2007). Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J Clin Invest 117, 2638–2648.
Graff, J.R. and Zimmer, S.G. (2003). Translational control and metastatic progression: enhanced activity of the mRNA cap-binding protein eIF-4E selectively enhances translation of metastasis-related mRNAs. Clin Exp Metastasis 20, 265–273.
Gregory, P.A., Bracken, C.P., Bert, A.G., and Goodall, G.J. (2008). MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle 7, 3112–3118.
Grifo, J.A., Abramson, R.D., Satler, C.A., and Merrick, W.C. (1984). RNA-stimulated ATPase activity of eukaryotic initiation factors. J Biol Chem 259, 8648–8654.
Gu, X., Jones, L., Lowery-Norberg, M., and Fowler, M. (2005). Expression of eukaryotic initiation factor 4E in astrocytic tumors. Appl Immunohistochem Mol Morphol 13, 178–183.
Guertin, D.A. and Sabatini, D.M. (2007). Defining the role of mTOR in cancer. Cancer Cell 12, 9–22.
Hadad, S.M., Fleming, S., and Thompson, A.M. (2008). Targeting AMPK: a new therapeutic opportunity in breast cancer. Crit Rev Oncol Hematol 67, 1–7.
Harada, H., Itasaka, S., Zhu, Y., et al. (2009). Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy. Br J Cancer 100, 747–757.
Harris, M.N., Ozpolat, B., Abdi, F., et al. (2004). Comparative proteomic analysis of all-trans-retinoic acid treatment reveals systematic posttranscriptional control mechanisms in acute promyelocytic leukemia. Blood 104, 1314–1323.
Hermeking, H. (2009). MiR-34a and p53. Cell Cycle 8, 1308.
Hershey, J.W.B. and Merrick, W.C. (2000). The pathway and mechanism of initiation of protein synthesis. In Sonenberg, N., Hershey, J.W.B., and Mathews, M.B. (eds.) Translational Control of Gene Expression. New York: Cold Spring Harbor Laboratory Press, pp. 33–88.
Hiller, D.J., Chu, Q., Meschonat, C., et al. (2009). Predictive value of eIF4E reduction after neoadjuvant therapy in breast cancer. J Surg Res 156, 265–269.
Holland, E.C. (2004). Regulation of translation and cancer. Cell Cycle 3, 452–455.
Holland, E.C., Sonenberg, N., Pandolfi, P.P., and Thomas, G. (2004). Signaling control of mRNA translation in cancer pathogenesis. Oncogene 23, 3138–3144.
Holz, M.K., Ballif, B.A., Gygi, S.P., and Blenis, J. (2005). mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 123, 569–580.
Hsieh, A.C., Costa, M., Zollo, O., et al. (2010). Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E. Cancer Cell 17, 249–261.
Inoki, K., Ouyang, H., Li, Y., and Guan, K.L. (2005). Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev 69, 79–100.
Ji, J. and Zheng, P.S. (2010). Activation of mTOR signaling pathway contributes to survival of cervical cancer cells. Gynecol Oncol 117, 103–108.
Jiang, B.H. and Liu, L.Z. (2008). Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment. Drug Resist Updat 11, 63–76.
Jiang, H., Coleman, J., Miskimins, R., and Miskimins, W.K. (2003). Expression of constitutively active 4EBP-1 enhances p27Kip1 expression and inhibits proliferation of MCF7 breast cancer cells. Cancer Cell Int 3, 2.
Jiang, H.Y. and Wek, R.C. (2005). Phosphorylation of eIF2alpha reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. J Biol Chem 280, 14189–14202.
Kao, C.L., Hsu, H.S., Chen, H.W., and Cheng, T.H. (2009). Rapamycin increases the p53/MDM2 protein ratio and p53-dependent apoptosis by translational inhibition of mdm2 in cancer cells. Cancer Lett 286, 250–259.
Kawauchi, K., Ogasawara, T., Yasuyama, M., Otsuka, K., and Yamada, O. (2009). Regulation and importance of the PI3K/Akt/mTOR signaling pathway in hematologic malignancies. Anticancer Agents Med Chem 9, 1024–1038.
Kentsis, A., Topisirovic, I., Culjkovic, B., Shao, L., and Borden, K.L.B. (2004). Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci USA 101, 18105–18110.
Khan, M.A. and Goss, D.J. (2004). Phosphorylation states of translational initiation factors affect mRNA cap binding in wheat. Biochemistry 43, 9092–9097.
Kim, S.H., Miller, F.R., Tait, L., Zheng, J., and Novak, R.F. (2009). Proteomic and phosphoproteomic alterations in benign, premalignant and tumor human breast epithelial cells and xenograft lesions: biomarkers of progression. Int J Cancer 124, 2813–2828.
Ko, S.Y., Guo, H., Barengo, N., and Naora, H. (2009). Inhibition of ovarian cancer growth by a tumor-targeting peptide that binds eukaryotic translation initiation factor 4E. Clin Cancer Res 15, 4336–4347.
Kodali, D., Rawal, A., Ninan, M.J., et al. (2011). Expression and phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 in B-cell lymphomas and reactive lymphoid tissues. Arch Pathol Lab Med 135, 365–371.
Komar, A.A. and Hatzoglou, M. (2005). Internal ribosome entry sites in cellular mRNAs: mystery of their existence. J Biol Chem 280, 23425–23428.
Konicek, B.W., Dumstorf, C.A., and Graff, J.R. (2008). Targeting the eIF4F translation initiation complex for cancer therapy. Cell Cycle 7, 2466–2471.
Konicek, B.W., Stephens, J.R., McNulty, A.M., et al. (2011). Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases. Cancer Res 71, 1849–1857.
Korneeva, N.L., Lamphear, B.J., Hennigan, F.L.C., and Rhoads, R.E. (2000). Mutually cooperative binding of eukaryotic translation initiation factor (eIF) 3 and eIF4A to human eIF4G-1. J Biol Chem 275, 41369–41376.
Koromilas, A.E., Lazaris-Karatzas, A., and Sonenberg, N. (1992). mRNAs containing extensive secondary structure in their 5′ non-coding region translate efficiently in cells overexpressing initiation factor eIF-4E. EMBO J 11, 4153–4158.
Kremer, C.L., Klein, R.R., Mendelson, J., et al. (2006). Expression of mTOR signaling pathway markers in prostate cancer progression. Prostate 66, 1203–1212.
Land, S.C. and Tee, A.R. (2007). Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem 282, 20534–20543.
Lane, H.A. and Breuleux, M. (2009). Optimal targeting of the mTORC1 kinase in human cancer. Curr Opin Cell Biol 21, 219–229.
Lee, J.W., Choi, J.J., Lee, K.M., et al. (2005). eIF-4E expression is associated with histopathologic grades in cervical neoplasia. Hum Pathol 36, 1197–1203.
Li, S., Perlman, D.M., Peterson, M.S., et al. (2004). Translation initiation factor 4E blocks endoplasmic reticulum-mediated apoptosis. J Biol Chem 279, 21312–21317.
Li, S., Sonenberg, N., Gingras, A.C., et al. (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.
Li, S., Takasu, T., Perlman, D.M., et al. (2003). Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release. J Biol Chem 278, 3015–3022.
Lin, C.J., Cencic, R., Mills, J.R., Robert, F., and Pelletier, J. (2008). c-Myc and eIF4F are components of a feedforward loop that links transcription and translation. Cancer Res 68, 5326–5334.
Linder, P., Lasko, P.F., Ashburner, M., et al. (1989). Birth of the D-E-A-D box. Nature 337, 121–122.
Loh, P.G., Yang, H.S., Walsh, M.A., et al. (2009). Structural basis for translational inhibition by the tumour suppressor Pdcd4. EMBO J 28, 274–285.
Lu, P.D., Jousse, C., Marciniak, S.J., et al. (2004). Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2. EMBO J 23, 169–179.
Lu, Z., Liu, M., Stribinskis, V., et al. (2008). MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 27, 4373–4379.
Lundstrom, K. (2004). Gene therapy applications of viral vectors. Technol Cancer Res Treat 3, 467–477.
Lynch, M., Fitzgerald, C., Johnston, K.A., Wang, S.P., and Schmidt, E.V. (2004). Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth. J Biol Chem 279, 3327–3339.
Ma, L. and Weinberg, R.A. (2008). Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet 24, 448–456.
Majumder, P.K., Febbo, P.G., Bikoff, R., et al. (2004). mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 10, 594–601.
Mamane, Y., Petroulakis, E., LeBacquer, O., and Sonenberg, N. (2006). mTOR, translation initiation and cancer. Oncogene 25, 6416–6422.
Mamane, Y., Petroulakis, E., Rong, L.W., et al. (2004). eIF4E – from translation to transformation. Oncogene 23, 3172–3179.
Marcotrigiano, J., Gingras, A.C., Sonenberg, N., and Burley, S.K. (1999). Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of elF4G. Mol Cell 3, 707–716.
Martin, M.E., Perez, M.I., Redondo, C., et al. (2000). 4E binding protein 1 expression is inversely correlated to the progression of gastrointestinal cancers. Int J Biochem Cell Biol 32, 633–642.
Mavrakis, K.J. and Wendel, H.G. (2008). Translational control and cancer therapy. Cell Cycle 7, 2791–2794.
Mavrakis, K.J., Zhu, H., Silva, R.L., et al. (2008). Tumorigenic activity and therapeutic inhibition of Rheb GTPase. Genes Dev 22, 2178–2188.
Mayeur, G.L. and Hershey, J.W.B. (2002). Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e). FEBS Lett 514, 49–54.
McClusky, D.R., Chu, Q., Yu, H., et al. (2005). A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-positive breast cancer. Ann Surg 242, 584–590.
McEwen, E., Kedersha, N., Song, B., et al. (2005). Heme-regulated inhibitor kinase-mediated phosphorylation of eukaryotic translation initiation factor 2 inhibits translation, induces stress granule formation, and mediates survival upon arsenite exposure. J Biol Chem 280, 16925–16933.
McKendrick, L., Morley, S.J., Pain, V.M., Jagus, R., and Joshi, B. (2001). Phosphorylation of eukaryotic initiation factor 4E (eIF4E) at Ser209 is not required for protein synthesis in vitro and in vivo. Eur J Biochem 268, 5375–5385.
Merrick, W.C. (2004). Cap-dependent and cap-independent translation in eukaryotic systems. Gene 332, 1–11.
Miluzio, A., Beugnet, A., Volta, V., and Biffo, S. (2009). Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation. EMBO Rep 10, 459–465.
Mishra, R., Miyamoto, M., Yoshioka, T., et al. (2009). Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo. Int J Oncol 34, 1231–1240.
Moerke, N.J., Aktas, H., Chen, H., et al. (2007). Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 128, 257–267.
Mohr, I. (2005). To replicate or not to replicate: achieving selective oncolytic virus replication in cancer cells through translational control. Oncogene 24, 7697–7709.
Morley, S.J. (2001). The regulation of eIF4F during cell growth and cell death. Prog Mol Subcell Biol 27, 1–37.
Morley, S.J., Coldwell, M.J., and Clemens, M.J. (2005). Initiation factor modifications in the preapoptotic phase. Cell Death Differ 12, 571–584.
Morley, S.J. and Naegele, S. (2002). Phosphorylation of eukaryotic initiation factor (eIF) 4E is not required for de novo protein synthesis following recovery from hypertonic stress in human kidney cells. J Biol Chem 277, 32855–32859.
Nathan, C.O., Amirghahari, N., Abreo, F., et al. (2004). Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway. Clin Cancer Res 10, 5820–5827.
O'Reilly, T., McSheehy, P.M., Wartmann, M., et al. (2011). Evaluation of the mTOR inhibitor, everolimus, in combination with cytotoxic antitumor agents using human tumor models in vitro and in vivo. Anticancer Drugs 22, 58–78.
Oridate, N., Kim, H.J., Xu, X., and Lotan, R. (2005). Growth inhibition of head and neck squamous carcinoma cells by small interfering RNAs targeting eIF4E or cyclin D1 alone or combined with cisplatin. Cancer Biol Ther 4, 318–323.
Othumpangat, S., Kashon, M., and Joseph, P. (2005). Sodium arsenite-induced inhibition of eukaryotic translation initiation factor 4E (eIF4E) results in cytotoxicity and cell death. Mol Cell Biochem 279, 123–131.
Paglin, S., Lee, N.Y., Nakar, C., et al. (2005). Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells. Cancer Res 65, 11061–11070.
Panner, A., James, C.D., Berger, M.S., and Pieper, R.O. (2005). mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells. Mol Cell Biol 25, 8809–8823.
Panner, A., Parsa, A.T., and Pieper, R.O. (2006). Translational regulation of TRAIL sensitivity. Cell Cycle 5, 147–150.
Panwalkar, A., Verstovsek, S., and Giles, F.J. (2004). Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer 100, 657–666.
Parsa, A.T. and Holland, E.C. (2004). Cooperative translational control of gene expression by Ras and Akt in cancer. Trends Mol Med 10, 607–613.
Pataer, A., Swisher, S.G., Roth, J.A., Logothetis, C.J., and Corn, P. (2009). Inhibition of RNA-dependent protein kinase (PKR) leads to cancer cell death and increases chemosensitivity. Cancer Biol Ther 8.
Pause, A., Methot, N., Svitkin, Y., Merrick, W.C., and Sonenberg, N. (1994). Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation. EMBO J 13, 1205–1215.
Peidis, P., Papadakis, A.I., Muaddi, H., Richard, S., and Koromilas, A.E. (2011). Doxorubicin bypasses the cytoprotective effects of eIF2alpha phosphorylation and promotes PKR-mediated cell death. Cell Death Differ 18, 145–154.
Perkins, D.J. and Barber, G.N. (2004). Defects in translational regulation mediated by the ɑ subunit of eukaryotic initiation factor 2 inhibit antiviral activity and facilitate the malignant transformation of human fibroblasts. Mol Cell Biol 24, 2025–2040.
Peter, M.E. (2009). Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 8, 843–852.
Peterson, T.R., Laplante, M., Thoreen, C.C., et al. (2009). DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 137, 873–886.
Pickering, B.M. and Willis, A.E. (2005). The implications of structured 5′ untranslated regions on translation and disease. Semin Cell Dev Biol 16, 39–47.
Polak, P. and Hall, M.N. (2009). mTOR and the control of whole body metabolism. Curr Opin Cell Biol 21, 209–218.
Polunovsky, V.A., Gingras, A.C., Sonenberg, N., et al. (2000). Translational control of the antiapoptotic function of Ras. J Biol Chem 275, 24776–24780.
Pradelli, L.A., Beneteau, M., Chauvin, C., et al. (2010). Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation. Oncogene 29, 1641–1652.
Proud, C.G. (2005a). eIF2 and the control of cell physiology. Semin Cell Dev Biol 16, 3–12.
Proud, C.G. (2005b). The eukaryotic initiation factor 4E-binding proteins and apoptosis. Cell Death Differ 12, 541–546.
Ramirez-Valle, F., Braunstein, S., Zavadil, J., Formenti, S.C., and Schneider, R.J. (2008). eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy. J Cell Biol 181, 293–307.
Rasmussen, S.B., Kordon, E., Callahan, R., and Smith, G.H. (2001). Evidence for the transforming activity of a truncated Int6 gene, in vitro. Oncogene 20, 5291–5301.
Raught, B. and Gingras A.-C. (2007). Signaling to translation initiation. In Mathews, M.B., Sonenberg, N., and Hershey, J.W.B. (eds.) Translational Control in Biology and Medicine. New York: Cold Spring Harbor Laboratory Press, pp. 369–400.
Raught, B., Gingras, A.C., Gygi, S.P., et al. (2000). Serum-stimulated, rapamycin-sensitive phosphorylation sites in the eukaryotic translation initiation factor 4GI. EMBO J 19, 434–444.
Renner, O., Fominaya, J., Alonso, S., et al. (2007). Mst1, RanBP2 and eIF4G are new markers for in vivo PI3K activation in murine and human prostate. Carcinogenesis 28, 1418–1425.
Richter-Cook, N.J., Dever, T.E., Hensold, J.O., and Merrick, W.C. (1998). Purification and characterization of a new eukaryotic protein translation factor – eukaryotic initiation factor 4H. J Biol Chem 273, 7579–7587.
Robert, F. and Pelletier, J. (2009). Translation initiation: a critical signalling node in cancer. Expert Opin Ther Targets 13, 1279–1293.
Rosenwald, I.B. (2004). The role of translation in neoplastic transformation from a pathologist's point of view. Oncogene 23, 3230–3247.
Rosenwald, I.B., Wang, S.T., Savas, L., Woda, B., and Pullman, J. (2003). Expression of translation initiation factor eIF-2ɑ is increased in benign and malignant melanocytic and colonic epithelial neoplasms. Cancer 98, 1080–1088.
Rousseau, D., Gingras, A.C., Pause, A., and Sonenberg, N. (1996a). The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth. Oncogene 13, 2415–2420.
Rousseau, D., Kaspar, R., Rosenwald, I., Gehrke, L., and Sonenberg, N. (1996b). Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc Natl Acad Sci USA 93, 1065–1070.
Rowinsky, E.K. (2004). Targeting the molecular target of rapamycin (mTOR). Curr Opin Oncol 16, 564–575.
Ruggero, D. (2009). The role of Myc-induced protein synthesis in cancer. Cancer Res 69, 8839–8843.
Ruggero, D., Montanaro, L., Ma, L., et al. (2004). The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med 10, 484–486.
Ruggero, D. and Sonenberg, N. (2005). The Akt of translational control. Oncogene 24, 7426–7434.
Santhanam, A.N., Bindewald, E., Rajasekhar, V.K., et al. (2009). Role of 3′UTRs in the translation of mRNAs regulated by oncogenic eIF4E: a computational inference. PLoS One 4, e4868.
Sanvito, F., Vivoli, F., Gambini, S., et al. (2000). Expression of a highly conserved protein, p27BBP, during the progression of human colorectal cancer. Cancer Res 60, 510–516.
Schalm, S.S., Fingar, D.C., Sabatini, D.M., and Blenis, J. (2003). TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol 13, 797–806.
Schewe, D.M. and Aguirre-Ghiso, J.A. (2009). Inhibition of eIF2alpha dephosphorylation maximizes bortezomib efficiency and eliminates quiescent multiple myeloma cells surviving proteasome inhibitor therapy. Cancer Res 69, 1545–1552.
Schneider, R. and Sonenberg N. (2007). Translational control in cancer development and progression. In Mathews, M.B., Sonenberg, N., and Hershey, J.W.B. (eds.) Translational Control in Biology and Medicine. New York: Cold Spring Harbor Laboratory Press, pp. 401–431.
Schneider, R.J. and Mohr, I. (2003). Translation initiation and viral tricks. Trends Biochem Sci 28, 130–136.
Shahbazian, D., Parsyan, A., Petroulakis, E., Hershey, J., and Sonenberg, N. (2010a). eIF4B controls survival and proliferation and is regulated by proto-oncogenic signaling pathways. Cell Cycle 9, 4106–4109.
Shahbazian, D., Parsyan, A., Petroulakis, E., et al. (2010b). Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B. Mol Cell Biol 30, 1478–1485.
Shahbazian, D., Roux, P.P., Mieulet, V., et al. (2006). The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. EMBO J 25, 2781–2791.
Shao, J.Y., Evers, B.M., and Sheng, H.M. (2004). Roles of phosphatidylinositol 3′-kinase and mammalian target of rapamycin/p70 ribosomal protein S6 kinase in K-Ras-mediated transformation of intestinal epithelial cells. Cancer Res 64, 229–235.
She, Q.B., Halilovic, E., Ye, Q., et al. (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.
Shi, Y., Sharma, A., Wu, H., Lichtenstein, A., and Gera, J. (2005). Cyclin D1 and c-myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK- and ERK-dependent pathway. J Biol Chem 280, 10964–10973.
Shuda, M., Kondoh, N., Tanka, K., Ryo, A., et al. (2000). Enhanced expression of translation factor mRNAs in hepatocellular carcinoma. Anticancer Res 20, 2489–2494.
Silvera, D., Arju, R., Darvishian, F., Levine, P.H., et al. (2009). Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer. Nat Cell Biol 11, 903–908.
Silvera, D., Formenti, S.C., and Schneider, R.J. (2010). Translational control in cancer. Nat Rev Cancer 10, 254–266.
Silvera, D. and Schneider, R.J. (2009). Inflammatory breast cancer cells are constitutively adapted to hypoxia. Cell Cycle 8, 3091–3096.
Sonenberg, N. and Dever, T.E. (2003). Eukaryotic translation initiation factors and regulators. Curr Opin Struct Biol 13, 56–63.
Sonenberg, N. and Hinnebusch, A.G. (2007). New modes of translational control in development, behavior, and disease. Mol Cell 28, 721–729.
Sonenberg, N. and Hinnebusch, A.G. (2009). Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731–745.
Soni, A., Akcakanat, A., Singh, G., et al. (2008). eIF4E knockdown decreases breast cancer cell growth without activating Akt signaling. Mol Cancer Ther 7, 1782–1788.
Sparks, C.A. and Guertin, D.A. (2010). Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene 29, 3733–3744.
Spriggs, K.A., Bushell, M., and Willis, A.E. (2010). Translational regulation of gene expression during conditions of cell stress. Mol Cell 40, 228–237.
Spriggs, K.A., Stoneley, M., Bushell, M., and Willis, A.E. (2008). Re-programming of translation following cell stress allows IRES-mediated translation to predominate. Biol Cell 100, 27–38.
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.
Suzuki, C., Garces, R.G., Edmonds, K.A., et al. (2008). PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proc Natl Acad Sci USA 105, 3274–3279.
Svitkin, Y.V., Herdy, B., Costa-Mattioli, M., et al. (2005). Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation. Mol Cell Biol 25, 10556–10565.
Tamburini, J., Green, A.S., Bardet, V., et al. (2009). Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia. Blood 114, 1618–1627.
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.
Teachey, D.T., Obzut, D.A., Cooperman, J., et al. (2006). The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL. Blood 107, 1149–1155.
Tee, A.R. and Blenis, J. (2005). mTOR, translational control and human disease. Semin Cell Dev Biol 16, 29–37.
Teleman, A.A., Chen, Y.W., and Cohen, S.M. (2005). 4E-BP functions as a metabolic brake used under stress conditions but not during normal growth. Genes Dev 19, 1844–1848.
Thoreen, C.C., Kang, S.A., Chang, J.W., et al. (2009b). An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 284, 8023–8032.
Topisirovic, I., Guzman, M.L., McConnell, M.J., et al. (2003). Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport impedes hematopoietic differentiation and contributes to leukemogenesis. Mol Cell Biol 23, 8992–9002.
Topisirovic, I., Ruiz-Gutierrez, M., and Borden, K.L.B. (2004). Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities. Cancer Res 64, 8639–8642.
Topisirovic, I., Siddiqui, N., and Borden, K.L. (2009a). The eukaryotic translation initiation factor 4E (eIF4E) and HuR RNA operons collaboratively regulate the expression of survival and proliferative genes. Cell Cycle 8, 960–961.
Topisirovic, I., Siddiqui, N., Lapointe, V.L., et al. (2009b). Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP. EMBO J 28, 1087–1098.
van Gorp, A.G., van der Vos, K.E., Brenkman, A.B., et al. (2009). AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B. Oncogene 28, 95–106.
van Riggelen, J., Yetil, A., and Felsher, D.W. (2010). MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10, 301–309.
Wang, R., Geng, J., Wang, J.H., et al. (2009). Overexpression of eukaryotic initiation factor 4E (eIF4E) and its clinical significance in lung adenocarcinoma. Lung Cancer 66, 237–244.
Wang, X. and Sun, S.Y. (2009). Enhancing mTOR-targeted cancer therapy. Expert Opin Ther Targets 13, 1193–1203.
Wang, X., Wei, Z., Gao, F., et al. (2008). Expression and prognostic significance of PDCD4 in human epithelial ovarian carcinoma. Anticancer Res 28, 2991–2996.
Watkins, S.J. and Norbury, C.J. (2002). Translation initiation and its deregulation during tumorigenesis. Br J Cancer 86, 1023–1027.
Wei, Z.T., Zhang, X., Wang, X.Y., et al. (2009). PDCD4 inhibits the malignant phenotype of ovarian cancer cells. Cancer Sci 100, 1408–1413.
Wendel, H.G., De Stanchina, E., Fridman, J.S., et al. (2004). Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 428, 332–337.
Wilker, E.W., van Vugt, M.A., Artim, S.A., et al. (2007). 14-3-3sigma controls mitotic translation to facilitate cytokinesis. Nature 446, 329–332.
Woodard, J., Sassano, A., Hay, N., and Platanias, L.C. (2008). Statin-dependent suppression of the Akt/mammalian target of rapamycin signaling cascade and programmed cell death 4 up-regulation in renal cell carcinoma. Clin Cancer Res 14, 4640–4649.
Wouters, B.G. and Koritzinsky, M. (2008). Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat Rev Cancer 8, 851–864.
Wu, C., Wangpaichitr, M., Feun, L., et al. (2005). Overcoming cisplatin resistance by mTOR inhibitor in lung cancer. Mol Cancer 4, 25.
Yang, H.S., Jansen, A.P., Komar, A.A., et al. (2003). The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol 23, 26–37.
Yin, J.Y., Dong, Z., Liu, Z.Q., and Zhang, J.T. (2010). Translational control gone awry: a new mechanism of tumorigenesis and novel targets of cancer treatments. Biosci Rep 31, 1–15.
Yoon, C.H., Lee, E.S., Lim, D.S., and Bae, Y.S. (2009). PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53. Proc Natl Acad Sci USA 106, 7852–7857.
Yu, D., Scott, C., Jia, W.W., et al. (2006). Targeting and killing of prostate cancer cells using lentiviral constructs containing a sequence recognized by translation factor eIF4E and a prostate-specific promoter. Cancer Gene Ther 13, 32–43.
Yu, K., Toral-Barza, L., Shi, C., et al. (2009). Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res 69, 6232–6240.
Zhang, L., Pan, X., and Hershey, J.W. (2007). Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells. J Biol Chem 282, 5790–5800.
Zhang, L., Smit-McBride, Z., Pan, X., Rheinhardt, J., and Hershey, J.W. (2008a). An oncogenic role for the phosphorylated h-subunit of human translation initiation factor eIF3. J Biol Chem 283, 24047–24060.
Zhang, M., Fu, W., Prabhu, S., et al. (2008b). Inhibition of polysome assembly enhances imatinib activity against chronic myelogenous leukemia and overcomes imatinib resistance. Mol Cell Biol 28, 6496–6509.
Zhu, N., Gu, L., Findley, H.W., and Zhou, M. (2005). Transcriptional repression of the eukaryotic initiation factor 4E gene by wild type p53. Biochem Biophys Res Commun 335, 1272–1279.
Zimmer, S.G., DeBenedetti, A., and Graff, J.R. (2000). Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a central regulator of tumor formation, growth, invasion and metastasis. Anticancer Res 20, 1343–1351.
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.