Mechanistic / mammalian target protein of rapamycin signaling in hematopoietic stem cells and leukemia

Cancer Science

Volumn 104, Issue 8, 2013, Pages 977-982

  Hirao, Atsushi ^a   Hoshii, Takayuki ^a  

^a KANAZAWA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; CYTARABINE; ETOPOSIDE; EVEROLIMUS; FK 506 BINDING PROTEIN; GROWTH FACTOR RECEPTOR BOUND PROTEIN 10; GUANOSINE TRIPHOSPHATASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN RECEPTOR SUBSTRATE 1; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOXANTRONE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAPAMYCIN; RIDAFOROLIMUS; TEMSIROLIMUS;

ACTIN FILAMENT; ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; AUTOPHAGY; B CELL LEUKEMIA; BIOGENESIS; BONE MARROW; CANCER COMBINATION CHEMOTHERAPY; CANCER INCIDENCE; CANCER STEM CELL; CELL ACTIVATION; CELL CYCLE G0 PHASE; CELL FUNCTION; CELL METABOLISM; CELL SHAPE; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CYTOTOXICITY; DISEASE ERADICATION; DNA MODIFICATION; DOWN REGULATION; DRUG DOSE ESCALATION; DRUG TARGETING; ENERGY METABOLISM; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME SUBSTRATE; FEEDBACK SYSTEM; GLUCOSE METABOLISM; GLYCOLYSIS; HEMATOLOGIC MALIGNANCY; HEMATOPOIETIC STEM CELL; HOMEOSTASIS; HUMAN; KIDNEY CARCINOMA; LEUKEMIA CELL; LEUKEMOGENESIS; LIPOGENESIS; LONG TERM CARE; MYELOPROLIFERATIVE DISORDER; NEGATIVE FEEDBACK; NONHUMAN; NUTRIENT AVAILABILITY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHILADELPHIA CHROMOSOME POSITIVE CELL; PHOSPHORYLATION; PRE B LYMPHOCYTE; PRIORITY JOURNAL; PROTEIN HOMEOSTASIS; PROTEIN SYNTHESIS; PROTEIN TARGETING; RECEPTOR DOWN REGULATION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; STEM CELL RESEARCH; STEROL SYNTHESIS; STRESS;

EID: 84881089754     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/cas.12189     Document Type: Review

References (67)

1. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730-7.
2. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-11.
3. Naka K, Hoshii T, Tadokoro Y, Hirao A. Molecular pathology of tumor-initiating cells: lessons from Philadelphia chromosome-positive leukemia. Pathol Int 2011; 61: 501-8.
4. Goardon N, Marchi E, Atzberger A et al. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell 2011; 19: 138-52.
5. Krivtsov AV, Twomey D, Feng Z et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006; 442: 818-22.
6. Somervaille TC, Matheny CJ, Spencer GJ et al. Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. Cell Stem Cell 2009; 4: 129-40.
7. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 2003; 17: 3029-35.
8. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 2009; 10: 307-18.
9. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149: 274-93.
10. Suda T, Takubo K, Semenza GL. Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell 2011; 9: 298-310.
11. Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 2003; 17: 1829-34.
12. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003; 13: 1259-68.
13. Thedieck K, Polak P, Kim ML et al. PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis. PLoS ONE 2007; 2: e1217.
14. Vander Haar E, Lee SI, Bandhakavi S, Griffin TJ, Kim DH. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol 2007; 9: 316-23.
15. Sancak Y, Thoreen CC, Peterson TR et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 2007; 25: 903-15.
16. Wang L, Harris TE, Roth RA, Lawrence JC Jr. PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem 2007; 282: 20036-44.
17. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005; 121: 179-93.
18. Inoki K, Ouyang H, Zhu T et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 2006; 126: 955-68.
19. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115: 577-90.
20. Gwinn DM, Shackelford DB, Egan DF et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008; 30: 214-26.
21. Brugarolas J, Lei K, Hurley RL et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 2004; 18: 2893-904.
22. DeYoung MP, Horak P, Sofer A, Sgroi D, Ellisen LW. Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling. Genes Dev 2008; 22: 239-51.
23. Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008; 10: 935-45.
24. Sancak Y, Peterson TR, Shaul YD et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008; 320: 1496-501.
25. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010; 141: 290-303.
26. Laplante M, Sabatini DM. An emerging role of mTOR in lipid biosynthesis. Curr Biol 2009; 19: R1046-52.
27. Horton JD, Goldstein JL, Brown MS. SREBPs: transcriptional mediators of lipid homeostasis. Cold Spring Harb Symp Quant Biol 2002; 67: 491-8.
28. Peterson TR, Sengupta SS, Harris TE et al. mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 2011; 146: 408-20.
29. Ramanathan A, Schreiber SL. Direct control of mitochondrial function by mTOR. Proc Natl Acad Sci USA 2009; 106: 22229-32.
30. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 2007; 450: 736-40.
31. Rabinowitz JD, White E. Autophagy and metabolism. Science 2010; 330: 1344-8.
32. Hosokawa N, Hara T, Kaizuka T et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20: 1981-91.
33. Hsu PP, Kang SA, Rameseder J et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 2011; 332: 1317-22.
34. Yu Y, Yoon SO, Poulogiannis G et al. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 2011; 332: 1322-6.
35. Zinzalla V, Stracka D, Oppliger W, Hall MN. Activation of mTORC2 by association with the ribosome. Cell 2011; 144: 757-68.
36. Jacinto E, Loewith R, Schmidt A et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004; 6: 1122-8.
37. Sarbassov DD, Ali SM, Kim DH et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 2004; 14: 1296-302.
38. Guertin DA, Stevens DM, Thoreen CC et al. 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 2006; 11: 859-71.
39. Jacinto E, Facchinetti V, Liu D et al. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 2006; 127: 125-37.
40. Naka K, Hirao A. Maintenance of genomic integrity in hematopoietic stem cells. Int J Hematol 2011; 93: 434-9.
41. Yamazaki S, Iwama A, Takayanagi S et al. Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells. EMBO J 2006; 25: 3515-23.
42. Miyamoto K, Araki KY, Naka K et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 2007; 1: 101-12.
43. Tothova Z, Kollipara R, Huntly BJ et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 2007; 128: 325-39.
44. Yalcin S, Zhang X, Luciano JP et al. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. J Biol Chem 2008; 283: 25692-705.
45. Chen C, Liu Y, Liu R, Ikenoue T, Guan KL, Zheng P. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med 2008; 205: 2397-408.
46. Gan B, Sahin E, Jiang S et al. TORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc Natl Acad Sci USA 2008; 105: 19384-9.
47. Chen C, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2009; 2: ra75.
48. Huang J, Nguyen-McCarty M, Hexner EO, Danet-Desnoyers G, Klein PS. Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways. Nat Med 2012; 18: 1778-85.
49. Yilmaz OH, Valdez R, Theisen BK et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 2006; 441: 475-82.
50. Zhang J, Grindley JC, Yin T et al. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 2006; 441: 518-22.
51. Lee JY, Nakada D, Yilmaz OH et al. mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion. Cell Stem Cell 2010; 7: 593-605.
52. Magee JA, Ikenoue T, Nakada D, Lee JY, Guan KL, Morrison CG. Temporal Changes in PTEN and mTORC2 regulation of hematopoietic stem cell self-renewal and leukemia suppression. Cell Stem Cell 2012; 11: 415-28.
53. Altman JK, Platanias LC. Exploiting the mammalian target of rapamycin pathway in hematologic malignancies. Curr Opin Hematol 2008; 15: 88-94.
54. Teachey DT, Grupp SA, Brown VI. Mammalian target of rapamycin inhibitors and their potential role in therapy in leukaemia and other haematological malignancies. Br J Haematol 2009; 145: 569-80.
55. Gutierrez A, Sanda T, Grebliunaite R et al. High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood 2009; 114: 647-50.
56. Sarbassov DD, Ali SM, Sengupta S et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159-68.
57. Kalaitzidis D, Sykes SM, Wang Z et al. mTOR complex 1 Plays critical roles in hematopoiesis and pten-loss-evoked leukemogenesis. Cell Stem Cell 2012; 11: 429-39.
58. Phung TL, Ziv K, Dabydeen D et al. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell 2006; 10: 159-70.
59. Yee KW, Zeng Z, Konopleva M et al. Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 2006; 12: 5165-73.
60. Perl AE, Kasner MT, Tsai DE et al. A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res 2009; 15: 6732-9.
61. Zent CS, LaPlant BR, Johnston PB et al. The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation. Cancer 2010; 116: 2201-7.
62. Rizzieri DA, Feldman E, Dipersio JF et al. A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 2008; 14: 2756-62.
63. Wang X, Beugnet A, Murakami M, Yamanaka S, Proud CG. Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins. Mol Cell Biol 2005; 25: 2558-72.
64. Choo AY, Yoon SO, Kim SG, Roux PP, Blenis J. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc Natl Acad Sci USA 2008; 105: 17414-9.
65. Janes MR, Limon JJ, So L et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med 2010; 16: 205-13.
66. Carayol N, Vakana E, Sassano A et al. Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. Proc Natl Acad Sci USA 2010; 107: 12469-74.
67. Hoshii T, Tadokoro Y, Naka K et al. mTORC1 is essential for leukemia propagation but not stem cell self-renewal. J Clin Invest 2012; 122: 2114-29.