Overcoming resistance to rapalogs in gliomas by combinatory therapies

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1834, Issue 7, 2013, Pages 1371-1380

  Grzmil, Michal ^a   Hemmings, Brian A ^a  

^a FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH   (Switzerland)

Author keywords

GBM; Kinase inhibitors; mTOR; Rapalog; Rapamycin

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; 1 [4 [1 (1,4 DIOXASPIRO[4.5]DEC 8 YL) 4 (8 OXA 3 AZABICYCLO[3.2.1]OCT 3 YL) 1H PYRAZOLO[3,4 D]PYRIMIDIN 6 YL]PHENYL] 3 METHYLUREA; 2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 2 (4 AMINO 1 ISOPROPYL 1H PYRAZOLO[3,4 D]PYRIMIDIN 3 YL) 1H INDOL 5 OL; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; ALPHA [AMINO(4 AMINOPHENYLTHIO)METHYLENE] 2 (TRIFLUOROMETHYL)PHENYLACETONITRILE; CGP 57380; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; GLYCOGEN SYNTHASE KINASE 3; HAMARTIN; IMMUNOMODULATING AGENT; KU 0063794; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MITOGEN ACTIVATED PROTEIN KINASE; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; NEUROFIBROMIN; PAXILLIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; RAF PROTEIN; RAPAMYCIN; RAPAMYCIN DERIVATIVE; RAS PROTEIN; RIDAFOROLIMUS; S6 KINASE; SCATTER FACTOR RECEPTOR; TEMSIROLIMUS; TUBERIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; UO 126; WNT PROTEIN;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ASTROCYTOMA; AUTOPHAGY; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER RESISTANCE; CARCINOGENESIS; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; CELL RENEWAL; CELL SURVIVAL; CLINICAL TRIAL (TOPIC); CYTOTOXICITY; DRUG EFFICACY; GENE EXPRESSION; GENE OVEREXPRESSION; GLIOBLASTOMA; GLIOMA; GLIOMA CELL; HISTOPATHOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LIPOGENESIS; MAMMAL; MEDULLOBLASTOMA; NEUROBLASTOMA; NONHUMAN; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN HYDROLYSIS; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; RECEPTOR DOWN REGULATION; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR XENOGRAFT;

ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; GLIOMA; HUMANS; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

MAMMALIA;

EID: 84878847083     PISSN: 15709639     EISSN: 18781454     Source Type: Journal    
DOI: 10.1016/j.bbapap.2013.01.041     Document Type: Review

References (142)

1. R. Stupp, F. Roila, and E.G.W. Group Malignant glioma: ESMO clinical recommendations for diagnosis, treatment and follow-up Ann. Oncol. 20 Suppl. 4 2009 126 128
2. T.A. Dolecek, J.M. Propp, N.E. Stroup, and C. Kruchko CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009 Neuro Oncol. 14 Suppl. 5 2012 v1 v49
3. M. Bower, E.S. Newlands, N.M. Bleehen, M. Brada, R.J. Begent, H. Calvert, I. Colquhoun, P. Lewis, and M.H. Brampton Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma Cancer Chemother. Pharmacol. 40 1997 484 488 (Pubitemid 27389289)
4. D. Osoba, M. Brada, W.K. Yung, and M. Prados Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme J. Clin. Oncol. 18 2000 1481 1491 (Pubitemid 30205394)
5. G. Lanzetta, C. Campanella, A. Rozzi, M. Nappa, A. Costa, F. Fedele, G. Innocenzi, F.M. Gagliardi, M. Salvati, G. Minniti, A. Frati, L. Frati, and A. Vecchione Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial Anticancer Res. 23 2003 5159 5164 (Pubitemid 38182140)
6. R. Stupp, W.P. Mason, M.J. van den Bent, M. Weller, B. Fisher, M.J. Taphoorn, K. Belanger, A.A. Brandes, C. Marosi, U. Bogdahn, J. Curschmann, R.C. Janzer, S.K. Ludwin, T. Gorlia, A. Allgeier, D. Lacombe, J.G. Cairncross, E. Eisenhauer, R.O. Mirimanoff, and R. European Organisation For, T. Treatment of Cancer Brain, G. Radiotherapy, G. National Cancer Institute of Canada Clinical Trials, Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N. Engl. J. Med. 352 2005 987 996
7. S.L. Gerson Clinical relevance of MGMT in the treatment of cancer J. Clin. Oncol. 20 2002 2388 2399 (Pubitemid 34441669)
8. M.E. Hegi, L. Liu, J.G. Herman, R. Stupp, W. Wick, M. Weller, M.P. Mehta, and M.R. Gilbert Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity J. Clin. Oncol. 26 2008 4189 4199
9. D.P. Houchens, A.A. Ovejera, S.M. Riblet, and D.E. Slagel Human brain tumor xenografts in nude mice as a chemotherapy model Eur. J. Cancer Clin. Oncol. 19 1983 799 805 (Pubitemid 13058375)
10. J. Kunz, R. Henriquez, U. Schneider, M. Deuter-Reinhard, N.R. Movva, and M.N. Hall Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression Cell 73 1993 585 596 (Pubitemid 23143356)
11. E.J. Brown, M.W. Albers, T.B. Shin, K. Ichikawa, C.T. Keith, W.S. Lane, and S.L. Schreiber A mammalian protein targeted by G1-arresting rapamycin-receptor complex Nature 369 1994 756 758
12. D.M. Sabatini, H. Erdjument-Bromage, M. Lui, P. Tempst, and S.H. Snyder RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs Cell 78 1994 35 43 (Pubitemid 24228298)
13. M. Laplante, and D.M. Sabatini mTOR signaling in growth control and disease Cell 149 2012 274 293
14. L. Wang, T.E. Harris, and J.C. Lawrence Jr. Regulation of proline-rich Akt substrate of 40 kDa (PRAS40) function by mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation J. Biol. Chem. 283 2008 15619 15627
15. S.M. McBride, D.A. Perez, M.Y. Polley, S.R. Vandenberg, J.S. Smith, S. Zheng, K.R. Lamborn, J.K. Wiencke, S.M. Chang, M.D. Prados, M.S. Berger, D. Stokoe, and D.A. Haas-Kogan Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival J. Neurooncol 97 2010 33 40
16. J. Masri, A. Bernath, J. Martin, O.D. Jo, R. Vartanian, A. Funk, and J. Gera mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor Cancer Res. 67 2007 11712 11720
17. T. Bashir, C. Cloninger, N. Artinian, L. Anderson, A. Bernath, B. Holmes, A. Benavides-Serrato, N. Sabha, R.N. Nishimura, A. Guha, and J. Gera Conditional astroglial Rictor overexpression induces malignant glioma in mice PLoS One 7 2012 e47741
18. D. Gao, H. Inuzuka, M.K. Tan, H. Fukushima, J.W. Locasale, P. Liu, L. Wan, B. Zhai, Y.R. Chin, S. Shaik, C.A. Lyssiotis, S.P. Gygi, A. Toker, L.C. Cantley, J.M. Asara, J.W. Harper, and W. Wei mTOR drives its own activation via SCF(betaTrCP)-dependent degradation of the mTOR inhibitor DEPTOR Mol. Cell 44 2011 290 303
19. N. Cancer Genome Atlas Research Comprehensive genomic characterization defines human glioblastoma genes and core pathways Nature 455 2008 1061 1068
20. M. Grzmil, and B.A. Hemmings Translation regulation as a therapeutic target in cancer Cancer Res. 72 2012 3891 3900
21. E. Fayard, L.A. Tintignac, A. Baudry, and B.A. Hemmings Protein kinase B/Akt at a glance J. Cell Sci. 118 2005 5675 5678 (Pubitemid 43079259)
22. D.D. Sarbassov, D.A. Guertin, S.M. Ali, and D.M. Sabatini Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex Science 307 2005 1098 1101 (Pubitemid 40262113)
23. V. Zinzalla, D. Stracka, W. Oppliger, and M.N. Hall Activation of mTORC2 by association with the ribosome Cell 144 2011 757 768
24. W.C. Hahn, C.M. Counter, A.S. Lundberg, R.L. Beijersbergen, M.W. Brooks, and R.A. Weinberg Creation of human tumour cells with defined genetic elements Nature 400 1999 464 468 (Pubitemid 29361801)
25. S. Belin, A. Beghin, E. Solano-Gonzalez, L. Bezin, S. Brunet-Manquat, J. Textoris, A.C. Prats, H.C. Mertani, C. Dumontet, and J.J. Diaz Dysregulation of ribosome biogenesis and translational capacity is associated with tumor progression of human breast cancer cells PLoS One 4 2009 e7147
26. X. Long, Y. Lin, S. Ortiz-Vega, K. Yonezawa, and J. Avruch Rheb binds and regulates the mTOR kinase Curr. Biol. 15 2005 702 713 (Pubitemid 40599924)
27. J. Avruch, K. Hara, Y. Lin, M. Liu, X. Long, S. Ortiz-Vega, and K. Yonezawa Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase Oncogene 25 2006 6361 6372 (Pubitemid 44596154)
28. E.M. Smith, S.G. Finn, A.R. Tee, G.J. Browne, and C.G. Proud The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses J. Biol. Chem. 280 2005 18717 18727 (Pubitemid 41379573)
29. D.J. Kwiatkowski, and B.D. Manning Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways Hum. Mol. Genet. 14 Spec No. 2 2005 R251 R258
30. M.N. Corradetti, K. Inoki, N. Bardeesy, R.A. DePinho, and K.L. Guan Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome Genes Dev. 18 2004 1533 1538 (Pubitemid 38868905)
31. D.A. Cross, D.R. Alessi, P. Cohen, M. Andjelkovich, and B.A. Hemmings Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B Nature 378 1995 785 789 (Pubitemid 26004411)
32. K. Inoki, H. Ouyang, T. Zhu, C. Lindvall, Y. Wang, X. Zhang, Q. Yang, C. Bennett, Y. Harada, K. Stankunas, C.Y. Wang, X. He, O.A. MacDougald, M. You, B.O. Williams, and K.L. Guan TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth Cell 126 2006 955 968 (Pubitemid 44310775)
33. U.D. Kahlert, D. Maciaczyk, S. Doostkam, B.A. Orr, B. Simons, T. Bogiel, T. Reithmeier, M. Prinz, J. Schubert, G. Niedermann, T. Brabletz, C.G. Eberhart, G. Nikkhah, and J. Maciaczyk Activation of canonical WNT/beta-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition Cancer Lett. 325 2012 42 53
34. X. Jin, H.Y. Jeon, K.M. Joo, J.K. Kim, J. Jin, S.H. Kim, B.G. Kang, S. Beck, S.J. Lee, J.K. Kim, A.K. Park, W.Y. Park, Y.J. Choi, D.H. Nam, and H. Kim Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation Cancer Res. 71 2011 3066 3075
35. X. Jiang, Y. Yu, H.W. Yang, N.Y. Agar, L. Frado, and M.D. Johnson The imprinted gene PEG3 inhibits Wnt signaling and regulates glioma growth J. Biol. Chem. 285 2010 8472 8480
36. H. Zheng, H. Ying, R. Wiedemeyer, H. Yan, S.N. Quayle, E.V. Ivanova, J.H. Paik, H. Zhang, Y. Xiao, S.R. Perry, J. Hu, A. Vinjamoori, B. Gan, E. Sahin, M.G. Chheda, C. Brennan, Y.A. Wang, W.C. Hahn, L. Chin, and R.A. DePinho PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas Cancer Cell 17 2010 497 509
37. Y. Sancak, C.C. Thoreen, T.R. Peterson, R.A. Lindquist, S.A. Kang, E. Spooner, S.A. Carr, and D.M. Sabatini PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase Mol. Cell 25 2007 903 915 (Pubitemid 46436534)
38. E. Vander Haar, S.I. Lee, S. Bandhakavi, T.J. Griffin, and D.H. Kim Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40 Nat. Cell Biol. 9 2007 316 323 (Pubitemid 46344611)
39. A. Guha Ras activation in astrocytomas and neurofibromas Can. J. Neurol. Sci. 25 1998 267 281 (Pubitemid 28516920)
40. L.T. McGillicuddy, J.A. Fromm, P.E. Hollstein, S. Kubek, R. Beroukhim, T. De Raedt, B.W. Johnson, S.M. Williams, P. Nghiemphu, L.M. Liau, T.F. Cloughesy, P.S. Mischel, A. Parret, J. Seiler, G. Moldenhauer, K. Scheffzek, A.O. Stemmer-Rachamimov, C.L. Sawyers, C. Brennan, L. Messiaen, I.K. Mellinghoff, and K. Cichowski Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis Cancer Cell 16 2009 44 54
41. L. Ma, Z. Chen, H. Erdjument-Bromage, P. Tempst, and P.P. Pandolfi Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis Cell 121 2005 179 193 (Pubitemid 40546387)
42. P.P. Roux, B.A. Ballif, R. Anjum, S.P. Gygi, and J. Blenis Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase Proc. Natl. Acad. Sci. U. S. A. 101 2004 13489 13494 (Pubitemid 39238430)
43. A. Carriere, M. Cargnello, L.A. Julien, H. Gao, E. Bonneil, P. Thibault, and P.P. Roux Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation Curr. Biol. 18 2008 1269 1277
44. E. Kim, P. Goraksha-Hicks, L. Li, T.P. Neufeld, and K.L. Guan Regulation of TORC1 by Rag GTPases in nutrient response Nat. Cell Biol. 10 2008 935 945
45. Y. Sancak, T.R. Peterson, Y.D. Shaul, R.A. Lindquist, C.C. Thoreen, L. Bar-Peled, and D.M. Sabatini The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 Science 320 2008 1496 1501 (Pubitemid 351929429)
46. Y. Sancak, L. Bar-Peled, R. Zoncu, A.L. Markhard, S. Nada, and D.M. Sabatini Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids Cell 141 2010 290 303
47. R. Zoncu, L. Bar-Peled, A. Efeyan, S. Wang, Y. Sancak, and D.M. Sabatini mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase Science 334 2011 678 683
48. N. Sonenberg, and A.G. Hinnebusch Regulation of translation initiation in eukaryotes: mechanisms and biological targets Cell 136 2009 731 745
49. M.R. Smith, M. Jaramillo, Y.L. Liu, T.E. Dever, W.C. Merrick, H.F. Kung, and N. Sonenberg Translation initiation factors induce DNA synthesis and transform NIH 3T3 cells New Biol. 2 1990 648 654 (Pubitemid 20330918)
50. A. De Benedetti, and J.R. Graff eIF-4E expression and its role in malignancies and metastases Oncogene 23 2004 3189 3199 (Pubitemid 38638830)
51. X. Gu, L. Jones, M. Lowery-Norberg, and M. Fowler Expression of eukaryotic initiation factor 4E in astrocytic tumors Appl. Immunohistochem. Mol. Morphol. 13 2005 178 183 (Pubitemid 40726856)
52. P. Korkolopoulou, G. Levidou, E.A. El-Habr, C. Piperi, C. Adamopoulos, V. Samaras, E. Boviatsis, I. Thymara, E.A. Trigka, S. Sakellariou, N. Kavantzas, E. Patsouris, and A.A. Saetta Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas Histopathology 61 2012 293 305
53. Y. Mamane, E. Petroulakis, Y. Martineau, T.A. Sato, O. Larsson, V.K. Rajasekhar, and N. Sonenberg Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation PLoS One 2 2007 e242
54. O. Larsson, S. Li, O.A. Issaenko, S. Avdulov, M. Peterson, K. Smith, P.B. Bitterman, and V.A. Polunovsky Eukaryotic translation initiation factor 4E induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors Cancer Res. 67 2007 6814 6824 (Pubitemid 47105529)
55. J. Chung, R.E. Bachelder, E.A. Lipscomb, L.M. Shaw, and A.M. Mercurio Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells J. Cell Biol. 158 2002 165 174
56. L. Furic, L. Rong, O. Larsson, I.H. Koumakpayi, K. Yoshida, A. Brueschke, E. Petroulakis, N. Robichaud, M. Pollak, L.A. Gaboury, P.P. Pandolfi, F. Saad, and N. Sonenberg eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression Proc. Natl. Acad. Sci. U. S. A. 107 2010 14134 14139
57. Y. Ge, F. Zhou, H. Chen, C. Cui, D. Liu, Q. Li, Z. Yang, G. Wu, S. Sun, J. Gu, Y. Wei, and J. Jiang Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells Biochem. Biophys. Res. Commun. 397 2010 711 717
58. C.G. Proud Signalling to translation: how signal transduction pathways control the protein synthetic machinery Biochem. J. 403 2007 217 234 (Pubitemid 46596577)
59. K. Boer, D. Troost, W. Timmermans, P.C. van Rijen, W.G. Spliet, and E. Aronica Pi3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors Brain Pathol. 20 2010 234 244
60. X.Y. Li, L.Q. Zhang, X.G. Zhang, X. Li, Y.B. Ren, X.Y. Ma, X.G. Li, and L.X. Wang Association between AKT/mTOR signalling pathway and malignancy grade of human gliomas J. Neurooncol 103 2011 453 458
61. T. Fukuchi-Shimogori, I. Ishii, K. Kashiwagi, H. Mashiba, H. Ekimoto, and K. Igarashi Malignant transformation by overproduction of translation initiation factor eIF4G Cancer Res. 57 1997 5041 5044 (Pubitemid 27498117)
62. C. Bauer, I. Diesinger, N. Brass, H. Steinhart, H. Iro, and E.U. Meese Translation initiation factor eIF-4G is immunogenic, overexpressed, and amplified in patients with squamous cell lung carcinoma Cancer 92 2001 822 829 (Pubitemid 32783068)
63. D. Silvera, R. Arju, F. Darvishian, P.H. Levine, L. Zolfaghari, J. Goldberg, T. Hochman, S.C. Formenti, and R.J. Schneider Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer Nat. Cell Biol. 11 2009 903 908
64. W.H. Shen, D.W. Boyle, P. Wisniowski, A. Bade, and E.A. Liechty Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids J. Endocrinol. 185 2005 275 289 (Pubitemid 40691794)
65. M. Dobrikov, E. Dobrikova, M. Shveygert, and M. Gromeier Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1) by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1 Mol. Cell. Biol. 31 2011 2947 2959
66. H.G. Wendel, R.L. Silva, A. Malina, J.R. Mills, H. Zhu, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, J. Teruya-Feldstein, J. Pelletier, and S.W. Lowe Dissecting eIF4E action in tumorigenesis Genes Dev. 21 2007 3232 3237 (Pubitemid 350277750)
67. M. Grzmil, P. Morin Jr., M.M. Lino, A. Merlo, S. Frank, Y. Wang, G. Moncayo, and B.A. Hemmings MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-beta signaling pathway in human glioblastoma Cancer Res. 71 2011 2392 2402
68. J.L. Nakamura, E. Garcia, and R.O. Pieper S6K1 plays a key role in glial transformation Cancer Res. 68 2008 6516 6523
69. X. Wang, W. Li, M. Williams, N. Terada, D.R. Alessi, and C.G. Proud Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase EMBO J. 20 2001 4370 4379 (Pubitemid 32772031)
70. D.M. Bagaglio, E.H. Cheng, F.S. Gorelick, K. Mitsui, A.C. Nairn, and W.N. Hait Phosphorylation of elongation factor 2 in normal and malignant rat glial cells Cancer Res. 53 1993 2260 2264 (Pubitemid 23156810)
71. H. Wu, J.M. Yang, S. Jin, H. Zhang, and W.N. Hait Elongation factor-2 kinase regulates autophagy in human glioblastoma cells Cancer Res. 66 2006 3015 3023
72. Y. Zhang, Y. Cheng, L. Zhang, X. Ren, K.J. Huber-Keener, S. Lee, J. Yun, H.G. Wang, and J.M. Yang Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression Biochem. Biophys. Res. Commun. 414 2011 129 134
73. F. Gao, P. Zhang, C. Zhou, J. Li, Q. Wang, F. Zhu, C. Ma, W. Sun, and L. Zhang Frequent loss of PDCD4 expression in human glioma: possible role in the tumorigenesis of glioma Oncol. Rep. 17 2007 123 128
74. A.B. Gaur, S.L. Holbeck, N.H. Colburn, and M.A. Israel Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo Neuro Oncol. 13 2011 580 590
75. N.V. Dorrello, A. Peschiaroli, D. Guardavaccaro, N.H. Colburn, N.E. Sherman, and M. Pagano S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth Science 314 2006 467 471 (Pubitemid 44628968)
76. H.S. Yang, A.P. Jansen, A.A. Komar, X. Zheng, W.C. Merrick, S. Costes, S.J. Lockett, N. Sonenberg, and N.H. Colburn The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation Mol. Cell. Biol. 23 2003 26 37 (Pubitemid 36008498)
77. A.P. Jansen, C.E. Camalier, and N.H. Colburn Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis Cancer Res. 65 2005 6034 6041 (Pubitemid 40994387)
78. M. Shiota, H. Izumi, A. Tanimoto, M. Takahashi, N. Miyamoto, E. Kashiwagi, A. Kidani, G. Hirano, D. Masubuchi, Y. Fukunaka, Y. Yasuniwa, S. Naito, S. Nishizawa, Y. Sasaguri, and K. Kohno Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth Cancer Res. 69 2009 3148 3156
79. A. Vichalkovski, E. Gresko, D. Hess, D.F. Restuccia, and B.A. Hemmings PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage Oncogene 29 2010 3554 3565
80. G. Xue, D.F. Restuccia, Q. Lan, D. Hynx, S. Dirnhofer, D. Hess, C. Ruegg, and B.A. Hemmings Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-beta signaling axes Cancer Discov. 2 2012 248 259
81. S.A. Mikheeva, A.M. Mikheev, A. Petit, R. Beyer, R.G. Oxford, L. Khorasani, J.P. Maxwell, C.A. Glackin, H. Wakimoto, I. Gonzalez-Herrero, I. Sanchez-Garcia, J.R. Silber, P.J. Horner, and R.C. Rostomily TWIST1 promotes invasion through mesenchymal change in human glioblastoma Mol. Cancer 9 2010 194
82. C. Mayer, and I. Grummt Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases Oncogene 25 2006 6384 6391 (Pubitemid 44582283)
83. A.A. Michels MAF1: a new target of mTORC1 Biochem. Soc. Trans. 39 2011 487 491
84. S. Levy, D. Avni, N. Hariharan, R.P. Perry, and O. Meyuhas Oligopyrimidine tract at the 5′ end of mammalian ribosomal protein mRNAs is required for their translational control Proc. Natl. Acad. Sci. U. S. A. 88 1991 3319 3323 (Pubitemid 21916612)
85. F. Loreni, G. Thomas, and F. Amaldi Transcription inhibitors stimulate translation of 5′ TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway Eur. J. Biochem. 267 2000 6594 6601
86. M. Laplante, and D.M. Sabatini An emerging role of mTOR in lipid biosynthesis Curr. Biol. 19 2009 R1046 R1052
87. T. Porstmann, C.R. Santos, B. Griffiths, M. Cully, M. Wu, S. Leevers, J.R. Griffiths, Y.L. Chung, and A. Schulze SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth Cell Metab. 8 2008 224 236
88. B.T. Wang, G.S. Ducker, A.J. Barczak, R. Barbeau, D.J. Erle, and K.M. Shokat The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile Proc. Natl. Acad. Sci. U. S. A. 108 2011 15201 15206
89. K. Duvel, J.L. Yecies, S. Menon, P. Raman, A.I. Lipovsky, A.L. Souza, E. Triantafellow, Q. Ma, R. Gorski, S. Cleaver, M.G. Vander Heiden, J.P. MacKeigan, P.M. Finan, C.B. Clish, L.O. Murphy, and B.D. Manning Activation of a metabolic gene regulatory network downstream of mTOR complex 1 Mol. Cell 39 2010 171 183
90. D. Guo, R.M. Prins, J. Dang, D. Kuga, A. Iwanami, H. Soto, K.Y. Lin, T.T. Huang, D. Akhavan, M.B. Hock, S. Zhu, A.A. Kofman, S.J. Bensinger, W.H. Yong, H.V. Vinters, S. Horvath, A.D. Watson, J.G. Kuhn, H.I. Robins, M.P. Mehta, P.Y. Wen, L.M. DeAngelis, M.D. Prados, I.K. Mellinghoff, T.F. Cloughesy, and P.S. Mischel EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy Sci. Signal. 2 2009 ra82
91. R.L. Jensen, B.T. Ragel, K. Whang, and D. Gillespie Inhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas J. Neurooncol 78 2006 233 247 (Pubitemid 44018816)
92. Y. Sonoda, M. Kanamori, D.F. Deen, S.Y. Cheng, M.S. Berger, and R.O. Pieper Overexpression of vascular endothelial growth factor isoforms drives oxygenation and growth but not progression to glioblastoma multiforme in a human model of gliomagenesis Cancer Res. 63 2003 1962 1968 (Pubitemid 36460864)
93. A. Marin-Hernandez, J.C. Gallardo-Perez, S.J. Ralph, S. Rodriguez-Enriquez, and R. Moreno-Sanchez HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms Mini Rev. Med. Chem. 9 2009 1084 1101
94. E.Y. Chan mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex Sci. Signal. 2 2009 e51
95. C. Settembre, R. Zoncu, D.L. Medina, F. Vetrini, S. Erdin, T. Huynh, M. Ferron, G. Karsenty, M.C. Vellard, V. Facchinetti, D.M. Sabatini, and A. Ballabio A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB EMBO J. 31 2012 1095 1108
96. S. Enzenmuller, P. Gonzalez, G. Karpel-Massler, K.M. Debatin, and S. Fulda GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma cells to lysosomal membrane permeabilization and cell death Cancer Lett. 329 2013 27 36
97. I.A. Ciechomska, K. Gabrusiewicz, A.A. Szczepankiewicz, and B. Kaminska Endoplasmic reticulum stress triggers autophagy in malignant glioma cells undergoing cyclosporine A-induced cell death Oncogene 2012 10.1038/onc.2012.174 (advance online publication 14 May 2012)
98. D. Wang, M.A. Olman, J. Stewart Jr., R. Tipps, P. Huang, P.W. Sanders, E. Toline, R.A. Prayson, J. Lee, R.J. Weil, C.A. Palmer, G.Y. Gillespie, W.M. Liu, R.O. Pieper, J.L. Guan, and C.L. Gladson Downregulation of FIP200 induces apoptosis of glioblastoma cells and microvascular endothelial cells by enhancing Pyk2 activity PLoS One 6 2011 e19629
99. E. Jacinto, V. Facchinetti, D. Liu, N. Soto, S. Wei, S.Y. Jung, Q. Huang, J. Qin, and B. Su SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity Cell 127 2006 125 137 (Pubitemid 44466632)
100. D.A. Guertin, D.M. Stevens, C.C. Thoreen, A.A. Burds, N.Y. Kalaany, J. Moffat, M. Brown, K.J. Fitzgerald, and D.M. Sabatini Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 Dev. Cell 11 2006 859 871 (Pubitemid 44804279)
101. A.B. da Rocha, D.R. Mans, A. Regner, and G. Schwartsmann Targeting protein kinase C: new therapeutic opportunities against high-grade malignant gliomas? Oncologist 7 2002 17 33 (Pubitemid 34151105)
102. A. Brunet, J. Park, H. Tran, L.S. Hu, B.A. Hemmings, and M.E. Greenberg Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a) Mol. Cell. Biol. 21 2001 952 965 (Pubitemid 32104742)
103. C.A. Mikosz, D.R. Brickley, M.S. Sharkey, T.W. Moran, and S.D. Conzen Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1 J. Biol. Chem. 276 2001 16649 16654
104. T. Kobayashi, and P. Cohen Activation of serum- and glucocorticoid- regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2 Biochem. J. 339 Pt 2 1999 319 328 (Pubitemid 29209961)
105. J. Park, M.L. Leong, P. Buse, A.C. Maiyar, G.L. Firestone, and B.A. Hemmings Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway EMBO J. 18 1999 3024 3033 (Pubitemid 29255611)
106. E. Jacinto, R. Loewith, A. Schmidt, S. Lin, M.A. Ruegg, A. Hall, and M.N. Hall Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive Nat. Cell Biol. 6 2004 1122 1128 (Pubitemid 39468014)
107. D.D. Sarbassov, S.M. Ali, S. Sengupta, J.H. Sheen, P.P. Hsu, A.F. Bagley, A.L. Markhard, and D.M. Sabatini Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB Mol. Cell 22 2006 159 168
108. C. Vezina, A. Kudelski, and S.N. Sehgal Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle J. Antibiot. (Tokyo) 28 1975 721 726
109. S.L. Schreiber Chemistry and biology of the immunophilins and their immunosuppressive ligands Science 251 1991 283 287 (Pubitemid 21916873)
110. J. Choi, J. Chen, S.L. Schreiber, and J. Clardy Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP Science 273 1996 239 242 (Pubitemid 26285890)
111. L.A. Banaszynski, C.W. Liu, and T.J. Wandless Characterization of the FKBP.rapamycin. FRB ternary complex J. Am. Chem. Soc. 127 2005 4715 4721 (Pubitemid 40489629)
112. F.J. Dumont, M.J. Staruch, T. Grammer, J. Blenis, C.A. Kastner, and K.M. Rupprecht Dominant mutations confer resistance to the immunosuppressant, rapamycin, in variants of a T cell lymphoma Cell. Immunol. 163 1995 70 79
113. D.A. Fruman, M.A. Wood, C.K. Gjertson, H.R. Katz, S.J. Burakoff, and B.E. Bierer FK506 binding protein 12 mediates sensitivity to both FK506 and rapamycin in murine mast cells Eur. J. Immunol. 25 1995 563 571
114. M.C. Lorenz, and J. Heitman TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin J. Biol. Chem. 270 1995 27531 27537
115. W. Schuler, R. Sedrani, S. Cottens, B. Haberlin, M. Schulz, H.J. Schuurman, G. Zenke, H.G. Zerwes, and M.H. Schreier SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo Transplantation 64 1997 36 42 (Pubitemid 27327197)
116. L.M. Ballou, and R.Z. Lin Rapamycin and mTOR kinase inhibitors J. Chem. Biol. 1 2008 27 36
117. B. Geoerger, K. Kerr, C.B. Tang, K.M. Fung, B. Powell, L.N. Sutton, P.C. Phillips, and A.J. Janss Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy Cancer Res. 61 2001 1527 1532 (Pubitemid 34292583)
118. E. Galanis, J.C. Buckner, M.J. Maurer, J.I. Kreisberg, K. Ballman, J. Boni, J.M. Peralba, R.B. Jenkins, S.R. Dakhil, R.F. Morton, K.A. Jaeckle, B.W. Scheithauer, J. Dancey, M. Hidalgo, and D.J. Walsh Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study J. Clin. Oncol. 23 2005 5294 5304 (Pubitemid 46206983)
119. S.M. Chang, P. Wen, T. Cloughesy, H. Greenberg, D. Schiff, C. Conrad, K. Fink, H.I. Robins, L. De Angelis, J. Raizer, K. Hess, K. Aldape, K.R. Lamborn, J. Kuhn, J. Dancey, and M.D. Prados Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme Invest. New Drugs 23 2005 357 361 (Pubitemid 40980358)
120. B. Geoerger, M.W. Kieran, S. Grupp, D. Perek, J. Clancy, M. Krygowski, R. Ananthakrishnan, J.P. Boni, A. Berkenblit, and S.L. Spunt Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma Eur. J. Cancer 48 2012 253 262
121. D.A. Krueger, M.M. Care, K. Holland, K. Agricola, C. Tudor, P. Mangeshkar, K.A. Wilson, A. Byars, T. Sahmoud, and D.N. Franz Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis N. Engl. J. Med. 363 2010 1801 1811
122. A.L. Mohan, M.D. Friedman, D.R. Ormond, M. Tobias, R. Murali, and M. Jhanwar-Uniyal PI3K/mTOR signaling pathways in medulloblastoma Anticancer Res. 32 2012 3141 3146
123. K. Yu, C. Shi, L. Toral-Barza, J. Lucas, B. Shor, J.E. Kim, W.G. Zhang, R. Mahoney, C. Gaydos, L. Tardio, S.K. Kim, R. Conant, K. Curran, J. Kaplan, J. Verheijen, S. Ayral-Kaloustian, T.S. Mansour, R.T. Abraham, A. Zask, and J.J. Gibbons Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2 Cancer Res. 70 2010 621 631
124. Q.W. Fan, and W.A. Weiss Inhibition of PI3K-Akt-mTOR signaling in glioblastoma by mTORC1/2 inhibitors Methods Mol. Biol. 821 2012 349 359
125. Y. Shi, H. Yan, P. Frost, J. Gera, and A. Lichtenstein 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 2005 1533 1540 (Pubitemid 41556435)
126. Q.W. Fan, Z.A. Knight, D.D. Goldenberg, W. Yu, K.E. Mostov, D. Stokoe, K.M. Shokat, and W.A. Weiss A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma Cancer Cell 9 2006 341 349 (Pubitemid 43668732)
127. Q.W. Fan, C.K. Cheng, T.P. Nicolaides, C.S. Hackett, Z.A. Knight, K.M. Shokat, and W.A. Weiss A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma Cancer Res. 67 2007 7960 7965 (Pubitemid 47395125)
128. S.M. Maira, F. Stauffer, J. Brueggen, P. Furet, C. Schnell, C. Fritsch, S. Brachmann, P. Chene, A. De Pover, K. Schoemaker, D. Fabbro, D. Gabriel, M. Simonen, L. Murphy, P. Finan, W. Sellers, and C. Garcia-Echeverria Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity Mol. Cancer Ther. 7 2008 1851 1863
129. T.J. Liu, D. Koul, T. LaFortune, N. Tiao, R.J. Shen, S.M. Maira, C. Garcia-Echevrria, and W.K. Yung NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas Mol. Cancer Ther. 8 2009 2204 2210
130. S. Guillard, P.A. Clarke, R. Te Poele, Z. Mohri, L. Bjerke, M. Valenti, F. Raynaud, S.A. Eccles, and P. Workman Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human glioma Cell Cycle 8 2009 443 453
131. J.S. Chen, L.J. Zhou, M. Entin-Meer, X. Yang, M. Donker, Z.A. Knight, W. Weiss, K.M. Shokat, D. Haas-Kogan, and D. Stokoe Characterization of structurally distinct, isoform-selective phosphoinositide 3′-kinase inhibitors in combination with radiation in the treatment of glioblastoma Mol. Cancer Ther. 7 2008 841 850 (Pubitemid 351551037)
132. B. Mukherjee, N. Tomimatsu, K. Amancherla, C.V. Camacho, N. Pichamoorthy, and S. Burma The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses Neoplasia 14 2012 34 43
133. A. Carracedo, L. Ma, J. Teruya-Feldstein, F. Rojo, L. Salmena, A. Alimonti, A. Egia, A.T. Sasaki, G. Thomas, S.C. Kozma, A. Papa, C. Nardella, L.C. Cantley, J. Baselga, and P.P. Pandolfi Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer J. Clin. Invest. 118 2008 3065 3074
134. S. Paternot, and P.P. Roger Combined inhibition of MEK and mammalian target of rapamycin abolishes phosphorylation of cyclin-dependent kinase 4 in glioblastoma cell lines and prevents their proliferation Cancer Res. 69 2009 4577 4581
135. J. Sunayama, K. Matsuda, A. Sato, K. Tachibana, K. Suzuki, Y. Narita, S. Shibui, K. Sakurada, T. Kayama, A. Tomiyama, and C. Kitanaka Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells Stem Cells 28 2010 1930 1939
136. J.P. Robinson, M.W. Vanbrocklin, K.J. Lastwika, A.J. McKinney, S. Brandner, and S.L. Holmen Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo Oncogene 30 2011 1341 1350
137. W.L. See, I.L. Tan, J. Mukherjee, T. Nicolaides, and R.O. Pieper Sensitivity of glioblastomas to clinically available MEK inhibitors is defined by neurofibromin 1 deficiency Cancer Res. 72 2012 3350 3359
138. X. Wang, P. Yue, C.B. Chan, K. Ye, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, H. Fu, F.R. Khuri, and S.Y. Sun Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation Mol. Cell. Biol. 27 2007 7405 7413 (Pubitemid 350033648)
139. Q.W. Fan, C. Cheng, C. Hackett, M. Feldman, B.T. Houseman, T. Nicolaides, D. Haas-Kogan, C.D. James, S.A. Oakes, J. Debnath, K.M. Shokat, and W.A. Weiss Akt and autophagy cooperate to promote survival of drug-resistant glioma Sci. Signal. 3 2010 ra81
140. M.A. Westhoff, J.A. Kandenwein, S. Karl, S.H. Vellanki, V. Braun, A. Eramo, G. Antoniadis, K.M. Debatin, and S. Fulda The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair Oncogene 28 2009 3586 3596
141. P.P. Hsu, S.A. Kang, J. Rameseder, Y. Zhang, K.A. Ottina, D. Lim, T.R. Peterson, Y. Choi, N.S. Gray, M.B. Yaffe, J.A. Marto, and D.M. Sabatini The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling Science 332 2011 1317 1322
142. Y. Yu, S.O. Yoon, G. Poulogiannis, Q. Yang, X.M. Ma, J. Villen, N. Kubica, G.R. Hoffman, L.C. Cantley, S.P. Gygi, and J. Blenis Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling Science 332 2011 1322 1326