Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway

British Journal of Cancer

Volumn 100, Issue 9, 2009, Pages 1406-1414

  Presneau, ^a,b   Shalaby, A ^a,b   Idowu, B ^b,c   Gikas, P ^c   Cannon, S R ^c   Gout, I ^b   Diss, T ^d   Tirabosco, R ^c   Flanagan, A M ^a,b,c  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c ROYAL NATIONAL ORTHOPAEDIC HOSPITAL   (United Kingdom)

^d UNIVERSITY COLLEGE HOSPITAL   (United Kingdom)

Author keywords

AKT; Brachyury; Chordoma; MTOR; Rapamycin

Indexed keywords

GENOMIC DNA; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAPAMYCIN; S6 KINASE; TENSIN; TUBERIN; CRTC2 PROTEIN, HUMAN; MTORC1 PROTEIN, HUMAN; TRANSCRIPTION FACTOR; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ADULT; AGED; ARTICLE; CHORDOMA; CONTROLLED STUDY; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE IDENTIFICATION; GENE LOCUS; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MALE; MOLECULAR DYNAMICS; MOLECULAR THERAPY; MOLECULE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; TISSUE MICROARRAY; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR GENE; WESTERN BLOTTING; DNA MICROARRAY; DRUG ANTAGONISM; GENETICS; METABOLISM; MIDDLE AGED; PATHOLOGY; PROTEIN MICROARRAY;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADULT; AGED; AGED, 80 AND OVER; BLOTTING, WESTERN; CHORDOMA; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION, FLUORESCENCE; MALE; MIDDLE AGED; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEIN ARRAY ANALYSIS; PROTO-ONCOGENE PROTEINS C-AKT; TRANSCRIPTION FACTORS; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS; YOUNG ADULT;

EID: 65549107687     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/sj.bjc.6605019     Document Type: Article

References (45)

1. Boulay A, Zumstein-Mecker S, Stephan C, Beuvink I, Zilbermann F, Haller R, Tobler S, Heusser C, O'Reilly T, Stolz B, Marti A, Thomas G, Lane HA (2004) Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RADOOl correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 64: 252-261
2. Casali PG, Stacchiotti S, Sangalli C, Olmi P, Gronchi A (2007) Chordoma. Curr Opin Oncol 19: 367-370
3. Cheng SW, Fryer LG, Carling D, Shepherd PR (2004) Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. J Biol Chem 279: 15719-15722
4. Cmejla R, Cmejlova J, Handrkova H, Petrak J, Petrtylova K, Mihal V, Stary J, Cerna Z, Jabali Y, Pospisilova D (2009) Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein LII (RPLIl) genes in Czech patients with Diamond-Blackfan anemia. Hum Mutat 30: 321-327
5. Downward J (2004) PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol 15: 177-182
6. Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tender D, Mohandas N, Carlsson B, Dahl N (1999) The gene encoding ribosomal protein S19 is mutated in Diamond - Blackfan anaemia. Afar Genet 21:169-175
7. El-Salem M, Raghunath PN, Marzec M, Wlodarski P, Tsai D, Hsi E, Wasik MA (2007) Constitutive activation of mTOR signaling pathway in posttransplant lymphoproliferative disorders. Lab Invest 87: 29-39
8. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM (2009) Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORCl and mTORC2. PIoS Biol 7: e38
9. Gao N, Zhang Z, Jiang BH, Shi X (2003) Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun 310: 1124-1132
10. Graff JR, Konicek BW, Carter JH, Marcusson EG (2008) Targeting the eukaryotic translation initiation factor 4E for cancer therapy. Cancer Res 68:631-634
11. Hallor KH, Staaf J, Jonsson G, Heidenblad M, VuIt von SF, Bauer HC, Ijszenga M, Hogendoorn PC, Mandahl N, Szuhai K, Mertens F (2008) Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. Br J Cancer 98: 434-442
12. Harada H, Andersen JS, Mann M, Terada N, Korsmeyer SJ (2001) p70S6 kinase signals cell survival as well as growth, inactivating the proapoptotic molecule BAD. Proc Natl Acad Sei USA 98: 9666-9670
13. Henderson SR, Guiliano D, Presneau N, McLean S, Frow R, Vujovic S, Anderson J, Sebire N, Whelan J, Athanasou N, Flanagan AM, Boshoff C (2005) A molecular map of mesenchymal tumors. Genome Biol 6: R76
14. Inoki K, Li Y, Zhu T, Wu J, Guan KL (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4: 648-657
15. Jaeschke A, Hartkamp J, Saitoh M, Roworth W, Nobukuni T, Hodges A, Sampson J, Thomas G, Lamb R (2002) Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent. J Cell Biol 159: 217-224
16. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110: 163-175
17. Krishnan K, Bruce B, Hewitt S, Thomas D, Khanna C, Helman LJ (2006) Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway. Clin Exp Metastasis 23: 227-236
18. Lee-Jones L, Aligianis I, Davies FA, Fuga A, Farndon PA, Stemmer-Rachamimov A, Ramesh V, Sampson JR (2004) Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSCl or TSC2. Genes Chromosomes Cancer 41: 80-85
19. Li Y, Inoki K, Guan KL (2004) Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. MoI Cell Biol 24: 7965-7975
20. Lu KH, Wu W, Dave B, Slomovitz BM, Burke TW, Munsell MF, Broaddus RR, Walker CL (2008) Loss of tuberous sclerosis complex-2 function and activation of mammalian target of rapamycin signaling in endometrial carcinoma. Clin Cancer Res 14: 2543-2550
21. MacKenzie AR, von Mehren M (2007) Mechanisms of mammalian target of rapamycin inhibition in sarcoma: present and future. Expert Rev Anticancer Ther7: 1145-1154
22. Martin DE, Hall MN (2005) The expanding TOR signaling network. Curt Opin Cell Biol 17: 158-166
23. Park L, Delaney TF, Liebsch NJ, Horniček FJ, Goldberg S, Mankin H, Rosenberg AE, Rosenthal DI, Suit HD (2006) Sacral chordomas: impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor. Int J Radiat Oncol Biol Phys 65: 1514-1521
24. Raught B, Feiretti F, Gingras AC, Livingstone M, Shahbazian D, Mayeur GL, Polakiewicz RD, Sonenberg N, Hershey JW (2004) Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases. EMBO J 23: 1761 -1769
25. Richardson CJ, Broenstrup M, Fingar DC, Julich K, Ballif BA, Gygi S, Blenis J (2004) SKAR is a specific target of S6 kinase 1 in cell growth control. CurrBiol 14: 1540-1549
26. Riemenschneider MJ, Betensky RA, Pasedag SM, Louis DN (2006) AKT activation in human glioblastomas enhances proliferation via TSC2 and S6 kinase signaling. Cancer Res 66: 5618-5623
27. Romeo S, Hogendoorn PC (2006) Brachyury and chordoma: the chondroid-chordoid dilemma resolved? / Pathol 209: 143-146
28. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (2004) Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sei USA 101: 13489-13494
29. Rowinsky EK (2004) Targeting the molecular target of rapamycin (mTOR). Curr Opin Oncol 16: 564-575
30. Rozeman LB, Szuhai K, Schrage YM, Rosenberg C, Tanke HJ, Taminiau AH, Cleton-Jansen AM, Bovee JV, Hogendoorn PC (2006) Array-comparative genomic hybridization of central chondrosarcoma: identification of ribosomal protein S6 and cyclin-dependent kinase 4 as candidate target genes for genomic aberrations. Cancer 107: 380-388
31. Ruvinsky I, Meyuhas O (2006) Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 31: 342-348
32. Ruvinsky I, Sharon N, Lerer T, Cohen H, Stolovich-Rain M, Nir T, Dor Y, Zisman P, Meyuhas O (2005) Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes Dev 19:2199-2211
33. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinder KW, Vogelstein B, Velculescu VE (2004) High frequency of mutations of the FIK3CA gene in human cancers. Science 304: 554
34. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, ErdjumentBromage H, Tempst P, Sabatini DM (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14: 1296-1302
35. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101
36. Scheil S, Bruderlein S, Liehr T, Starke H, Herms J, Schulte M, Moller P (2001) Genome-wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U-CHl. Genes Chromosomes Cancer 32: 203-211
37. Scheper MA, Chaisuparat R, Nikitakis NG, Sauk JJ (2008) Expression and alterations of the PTEN/AKT/mTOR pathway in ameloblastomas. Oral Dis 14: 561 -568
38. Tee AR, Blenis J, Proud CG (2005) Analysis of mTOR signaling by the small G-proteins, Rheb and RhebLl. FEBS Lett 579: 4763-4768
39. Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De MG, den Bakker MA, Di FL, Kalil RK, Athanasou NA, O'donnell P, McCarthy EF, Flanagan AM (2008) Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol 32: 572-580
40. Tkaczyk C, Metcalfe DD, Gilfillan AM (2002) Determination of protein phosphorylation in Fc epsilon RI-activated human mast cells by immunoblot analysis requires protein extraction under denaturing conditions. J Immunol Methods 268: 239-243
41. Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM (2006) Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 209: 157-165
42. Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124: 471-484
43. Yan L, Findlay GM, Jones R, Procter J, Cao Y, Lamb RF (2006) Hyperactivation of mammalian target of rapamycin (mTOR) signaling by a gain-of-function mutant of the Rheb GTPase. J Biol Chem 281:19793-19797
44. Yang Q, Inoki K, Ikenoue T, Guan KL (2006a) Identification of Sinl as an essential TORC2 component required for complex formation and kinase activity. Genes Dev 20: 2820-2832
45. Yang Q, Inoki K, Kim E, Guan KL (2006b) TSC1/TSC2 and Rheb have different effects on TORCl and TORC2 activity. Proc Natl Acad Sei USA 103:6811-6816