Integration of growth factor and nutrient signaling: Implications for cancer biology

Molecular Cell

Volumn 12, Issue 2, 2003, Pages 271-280

  Shamji, Alykhan F ^a   Nghiem, Paul ^b   Schreiber, Stuart L ^a  

^a HARVARD UNIVERSITY   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING PROTEIN; FK 506 BINDING PROTEIN; GROWTH FACTOR; INITIATION FACTOR 4E BINDING PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN; RAPAMYCIN; S6 KINASE; TARGET OF RAPAMYCIN KINASE; TEMSIROLIMUS; UNCLASSIFIED DRUG;

CANCER INHIBITION; CARCINOGENESIS; COWDEN SYNDROME; GENE MUTATION; HUMAN; NONHUMAN; NUTRIENT; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS;

EID: 0141923009     PISSN: 10972765     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molcel.2003.08.016     Document Type: Review

References (79)

1. Abraham R.T. Identification of TOR signaling complexes. more TORC for the cell growth engine Cell. 111:2002;9-12.
2. Biesecker L.G., Happle R., Mulliken J.B., Weksberg R., Graham J.M. Jr., Viljoen D.L., Cohen M.M. Jr. Proteus syndrome. diagnostic criteria, differential diagnosis, and patient evaluation Am. J. Med. Genet. 84:1999;389-395.
3. Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., Greenberg M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96:1999;857-868.
4. Burnett P.E., Barrow R.K., Cohen N.A., Snyder S.H., Sabatini D.M. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc. Natl. Acad. Sci. USA. 95:1998;1432-1437.
5. Cantley L.C., Neel B.G. New insights into tumor suppression. PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway Proc. Natl. Acad. Sci. USA. 96:1999;4240-4245.
6. Chattopadhyay S., Pearce D.A. Interaction with Btn2p is required for localization of Rsglp. Btn2p-mediated changes in arginine uptake in Saccharomyces cerevisiae Eukaryot. Cell. 1:2002;606-612.
7. Cheadle J.P., Reeve M.P., Sampson J.R., Kwiatkowski D.J. Molecular genetic advances in tuberous sclerosis. Hum. Genet. 107:2000;97-114.
8. Choi K.M., McMahon L.P., Lawrence J.C. Jr. Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian Target of Rapamycin and for recognition by Raptor. J. Biol. Chem. 278:2003;19667-19673.
9. Dan H.C., Sun M., Yang L., Feldman R.I., Sui X.M., Ou C.C., Nellist M., Yeung R.S., Halley D.J., Nicosia S.V.et al. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J. Biol. Chem. 277:2002;35364-35370.
10. Datta S.R., Dudek H., Tao X., Masters S., Fu H., Gotoh Y., Greenberg M.E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:1997;231-241.
11. Datta S.R., Katsov A., Hu L., Petros A., Fesik S.W., Yaffe M.B., Greenberg M.E. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol. Cell. 6:2000;41-51.
12. de Groot R.P., Ballou L.M., Sassone-Corsi P. Positive regulation of the cAMP-responsive activator CREM by the p70 S6 kinase. an alternative route to mitogen-induced gene expression Cell. 79:1994;81-91.
13. Dennis P.B., Jaeschke A., Saitoh M., Fowler B., Kozma S.C., Thomas G. Mammalian TOR. a homeostatic ATP sensor Science. 294:2001;1102-1105.
14. Desai B.N., Myers B.R., Schreiber S.L. FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA. 99:2002;4319-4324.
15. Fingar D.C., Salama S., Tsou C., Harlow E., Blenis J. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16:2002;1472-1487.
16. Gao X., Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15:2001;1383-1392.
17. Gao X., Zhang Y., Arrazola P., Hino O., Kobayashi T., Yeung R.S., Ru B., Pan D. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat. Cell Biol. 4:2002;699-704.
18. Garami A., Zwartkruis F.J.T., Nobukuni T., Joaquin M., Roccio M., Stocker H., Kozma S.C., Hafen E., Bos J.L., Thomas G. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and TSC2. Mol. Cell. 11:2003;1457-1466.
19. Gingras A.C., Raught B., Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 15:2001;807-826.
20. Grammer T.C., Cheatham L., Chou M.M., Blenis J. The p70S6K signalling pathway. a novel signalling system involved in growth regulation Cancer Surv. 27:1996;271-292.
21. Gromov P.S., Madsen P., Tomerup N., Celis J.E. A novel approach for expression cloning of small GTPases. identification, tissue distribution and chromosome mapping of the human homolog of rheb FEBS Lett. 377:1995;221-226.
22. Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S., Tokunaga C., Avruch J., Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 110:2002;177-189.
23. Hara K., Yonezawa K., Weng Q.P., Kozlowski M.T., Belham C., Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273:1998;14484-14494.
24. Harada H., Andersen J.S., Mann M., Terada N., Korsmeyer S.J. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc. Natl. Acad. Sci. USA. 98:2001;9666-9670.
25. Haruta T., Uno T., Kawahara J., Takano A., Egawa K., Sharma P.M., Olefsky J.M., Kobayashi M. A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol. Endocrinol. 14:2000;783-794.
26. Inoki K., Li Y., Zhu T., Wu J., Guan K.-L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4:2002;648-657.
27. Inoki K., Li Y., Xu T., Guan K.-L. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. in press.(Published online July 17):2003;2003. 0.1101/gad.1110003.
28. Jaeschke A., Hartkamp J., Saitoh M., Roworth W., Nobukuni T., Hodges A., Sampson J., Thomas G., Lamb R. Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent. J. Cell Biol. 159:2002;217-224.
29. Jain M., Arvanitis C., Chu K., Dewey W., Leonhardt E., Trinh M., Sundberg C.D., Bishop J.M., Felsher D.W. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science. 297:2002;102-104.
30. Kenerson H.L., Aicher L.D., True L.D., Yeung R.S. Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors. Cancer Res. 62:2002;5645-5650.
31. Kim D.H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 110:2002;163-175.
32. Kozma S.C., Thomas G. Regulation of cell size in growth, development and human disease. PI3K, PKB and S6K Bioessays. 24:2002;65-71.
33. Kuruvilla F.G., Schreiber S.L. The PIK-related kinases intercept conventional signaling pathways. Chem. Biol. 6:1999;R129-R136.
34. Kwiatkowski D.J., Zhang H., Bandura J.L., Heiberger K.M., Glogauer M., el-Hashemite N., Onda H. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum. Mol. Genet. 11:2002;525-534.
35. Lazaris-Karatzas A., Montine K.S., Sonenberg N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap. Nature. 345:1990;544-547.
36. Li Y., Inoki K., Yeung R., Guan K.-L. Regulation of TSC2 by 14-3-3 binding. J. Biol. Chem. 277:2002;44593-44596.
37. Liu M.Y., Cai S., Espejo A., Bedford M.T., Walker C.L. 14-3-3 interacts with the tumor suppressor tuberin at Akt phosphorylation site(s). Cancer Res. 62:2002;6475-6480.
38. Loewith R., Jacinto E., Wullschleger S., Lorberg A., Crespo J.L., Bonenfant D., Oppliger W., Jenoe P., Hall M.N. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell. 10:2002;457-468.
39. Mach K.E., Furge K.A., Albright C.F. Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics. 155:2000;611-622.
40. Maheshwar M.M., Cheadle J.P., Jones A.C., Myring J., Fryer A.E., Harris P.C., Sampson J.R. The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. Hum. Mol. Genet. 6:1997;1991-1996.
41. Manning B.D., Cantley L.C. United at last. the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling Biochem. Soc. Trans. 31:2003;573-578.
42. Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell. 10:2002;151-162.
43. Matsumoto S., Bandyopadhyay A., Kwiatkowski D.J., Maitra U., Matsumoto T. Role of the Tsc1-Tsc2 complex in signaling and transport across the cell membrane in the fission yeast Schizosaccharomyces pombe. Genetics. 161:2002;1053-1063.
44. Mills G.B., Lu Y., Kohn E.C. Linking molecular therapeutics to molecular diagnostics. inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo Proc. Natl. Acad. Sci. USA. 98:2001;10031-10033.
45. Miron M., Verdu J., Lachance P.E., Birnbaum M.J., Lasko P.F., Sonenberg N. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. Nat. Cell Biol. 3:2001;596-601.
46. Nave B.T., Ouwens M., Withers D.J., Alessi D.R., Shepherd P.R. Mammalian target of rapamycin is a direct target for protein kinase B. identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation Biochem. J. 344:1999;427-431.
47. Nellist M., Goedbloed M.A., De Winter C., Verhaaf B., Jankie A., Reuser A.J., Van Den Ouweland A.M., Van Der Sluijs P., Halley D.J. Identification and characterization of the interaction between tuberin and 14-3-3ζ J. Biol. Chem. 277:2002;39417-39424.
48. Nellist M., Goedbloed M.A., Halley D.J. Regulation of tuberous sclerosis complex (TSC) function by 14-3-3 proteins. Biochem. Soc. Trans. 31:2003;587-591.
49. Neshat M.S., Mellinghoff I.K., Tran C., Stiles B., Thomas G., Petersen R., Frost P., Gibbons J.J., Wu H., Sawyers C.L. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl. Acad. Sci. USA. 98:2001;10314-10319.
50. Nojima H., Tokunaga C., Eguchi S., Oshiro N., Hidayat S., Yoshino K., Hara K., Tanaka N., Avruch J., Yonezawa K. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J. Biol. Chem. 278:2003;15461-15464.
51. Pelengaris S., Khan M., Evan G. c-myc. more than just a matter of life and death Nat. Rev. Cancer. 2:2002;764-776.
52. Peterson R.T., Desai B.N., Hardwick J.S., Schreiber S.L. Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycin associated protein. Proc. Natl. Acad. Sci. USA. 96:1999;4438-4442.
53. Plas D.R., Thompson C.B. Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J. Biol. Chem. 278:2003;12361-12366.
54. Podsypanina K., Lee R.T., Politis C., Hennessy I., Crane A., Puc J., Neshat M., Wang H., Yang L., Gibbons J.et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc. Natl. Acad. Sci. USA. 98:2001;10320-10325.
55. Potter C.J., Pedraza L.G., Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4:2002;658-665.
56. Radimerski T., Montagne J., Rintelen F., Stocker H., van der Kaay J., Downes C.P., Hafen E., Thomas G. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat. Cell Biol. 4:2002;251-255.
57. Saucedo L.J., Gao X., Chiarelli D.A., Li L., Pan D., Edgar B.A. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 5:2003;566-571.
58. Schalm S.S., Blenis J. Identification of a conserved motif required for mTOR signaling. Curr. Biol. 12:2002;632-639.
59. Schalm S.S., Fingar D.C., Sabatini D.M., Blenis J. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr. Biol. 13:2003;797-806.
60. Sekulic A., Hudson C.C., Homme J.L., Yin P., Otterness D.M., Karnitz L.M., Abraham R.T. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 60:2000;3504-3513.
61. Shawver L.K., Slamon D., Ullrich A. Smart drugs. tyrosine kinase inhibitors in cancer therapy Cancer Cell. 1:2002;117-123.
62. Shumway S.D., Li Y., Xiong Y. 14-3-3β binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin. J. Biol. Chem. 278:2003;2089-2092.
63. Smith J.M., Kirk E.P., Theodosopoulos G., Marshall G.M., Walker J., Rogers M., Field M., Brereton J.J., Marsh D.J. Germline mutation of the tumour suppressor PTEN in Proteus syndrome. J. Med. Genet. 39:2002;937-940.
64. Soucek T., Rosner M., Miloloza A., Kubista M., Cheadle J.P., Sampson J.R., Hengstschlager M. Tuberous sclerosis causing mutants of the TSC2 gene product affect proliferation and p27 expression. Oncogene. 20:2001;4904-4909.
65. Stocker H., Radimerski T., Schindelholz B., Wittwer F., Belawat P., Daram P., Breuer S., Thomas G., Hafen E. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat. Cell Biol. 5:2003;559-566.
66. Stolovich M., Tang H., Hornstein E., Levy G., Cohen R., Bae S.S., Birnbaum M.J., Meyuhas O. Transduction of growth or mitogenic signals into translational activation of TOP mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but requires neither S6K1 nor rpS6 phosphorylation. Mol. Cell. Biol. 22:2002;8101-8113.
67. Tapon N., Moberg K.H., Hariharan I.K. The coupling of cell growth to the cell cycle. Curr. Opin. Cell Biol. 13:2001;731-737.
68. Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc. Natl. Acad. Sci. USA. 99:2002;13571-13576.
69. Tee A.R., Manning B.D., Roux P.P., Cantley L.C., Blenis J. Tuberous sclerosis gene products, tuberin and hamartin, control mTOR signaling by acting as a GTPase-acting protein complex toward Rheb. Curr. Biol. 13:2003;1259-1268.
70. Vivanco I., Sawyers C.L. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer. 2:2002;489-501.
71. Volarevic S., Thomas G. Role of S6 phosphorylation and S6 kinase in cell growth. Prog. Nucleic Acids Res. Mol. Biol. 265:2001;101-127.
72. Vogt P.K. PI 3-kinase, mTOR, protein synthesis and cancer. Trends Mol. Med. 7:2001;482-484.
73. Wang X., Li W., Williams M., Terada N., Alessi D.R., Proud C.G. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J. 20:2001;4370-4379.
74. Wataya-Kaneda M., Kaneda Y., Hino O., Adachi H., Hirayama Y., Seyama K., Satou T., Yoshikawa K. Cells derived from tuberous sclerosis show a prolonged S phase of the cell cycle and increased apoptosis. Arch. Dermatol. Res. 293:2001;460-469.
75. Weinstein I.B. Cancer. Addiction to oncogenes - the Achilles heel of cancer. Science. 297:2002;63-64.
76. Xia Y., Wen H.Y., Young M.E., Gurthrie P.H., Taegtmeyer H., Kellems R.E. mTOR and PKA signaling mediate the cardiac transcriptional response to glutamine. J. Biol. Chem. 278:2003;13143-13150.
77. Xu G., Kwon G., Cruz W.S., Marshall C.A., McDaniel M.L. Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic β-cells. Diabetes. 50:2001;353-360.
78. Yee W.M., Worley P.F. Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals. Mol. Cell. Biol. 17:1997;921-933.
79. Zhang Y., Gao X., Saucedo L.J., Ru B., Edgar B.A., Pan D. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5:2003;578-581.