Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor: Emerging insights into the molecular oncogenesis and treatment of Kaposi's sarcoma

Cell Cycle

Volumn 6, Issue 4, 2007, Pages 438-443

  Montaner, Silvia ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Akt; Human herpesvirus 8; Kaposi's sarcoma; Kaposi's sarcoma associated herpesvirus; mTOR; Rapamycin; Sirolimus; TSC; Viral G protein coupled receptor

Indexed keywords

CYCLOSPORIN; EVEROLIMUS; G PROTEIN COUPLED RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PROTEIN KINASE B; RAPAMYCIN; TEMSIROLIMUS; VIRUS PROTEIN;

CARCINOGENESIS; DISEASE COURSE; DRUG EFFICACY; GENE IDENTIFICATION; HERPES VIRUS; HUMAN; KAPOSI SARCOMA; MORBIDITY; MORTALITY; REVIEW;

ANIMALIA; HERPESVIRIDAE; HUMAN HERPESVIRUS 8;

EID: 33847779638     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.6.4.3843     Document Type: Review

References (70)

1. Boshoff C, Chang Y. Kaposi's sarcoma-associated herpesvirus: A new DNA tumor virus. Annu Rev Med 2001; 52:453-70.
2. Moore PS, Chang Y. Molecular virology of Kaposi's sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 2001; 356:499-516.
3. Pantanowitz L, Dezube BJ. Advances in the pathobiology and treatment of Kaposi sarcoma. Curr Opin Oncol 2004; 16:443-49.
4. Vanni T, Sprinz E, Machado MW, Santana Rde C, Fonseca BA, Schwartsmann G. Systemic treatment of AIDS-related Kaposi sarcoma: Current status and perspectives. Cancer Treat Rev 2006; 32:445-55.
5. Ganem D. Human herpesvirus 8 and its role in the genesis of Kaposi's sarcoma. Curr Clin Top Infect Dis 1998; 18:237-51.
6. Dourmishev LA, Dourmishev AL, Palmeri D, Schwartz RA, Lukac DM. Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis. Microbiol Mol Biol Rev 2003; 67:175-212.
7. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994; 266:1865-1869.
8. Cesarman E. The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. Recent Results Cancer Res 2002; 159:27-37.
9. Jenner RG, Boshoff C. The molecular pathology of Kaposi's sarcoma-associated herpesvirus. Biochim Biophys Acta 2002; 1602:1-22.
10. Schulz TF. Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8). J Gen Virol 1998; 79(Pt 7):1573-91.
11. Moore PS, Chang Y. Kaposi's sarcoma-associated herpesvirus-encoded oncogenes and oncogenesis. J Natl Cancer Inst Monogr 1998; 23:65-71.
12. Montaner S, Sodhi A, Molinolo A, et al. Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 2003; 3:23-36.
13. Guo HG, Sadowska M, Reid W, Tschachler E, Hayward G, Reitz M. Kaposi's sarcoma-like tumors in a human herpesvirus 8 ORF74 transgenic mouse. J Virol 2003; 77:2631-39.
14. Yang TY, Chen SC, Leach MW, et al. Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma. J Exp Med 2000; 191:445-54.
15. Sodhi A, Montaner S, Gutkind JS. Does dysregulated expression of a deregulated viral GPCR trigger Kaposi's sarcomagenesis? Faseb J 2004; 18:422-27.
16. Orem J, Otieno MW, Remick SC. AIDS-associated cancer in developing nations. Curr Opin Oncol 2004; 16:468-76.
17. Sodhi A, Montaner S, Gutkind JS. Viral hijacking of G-protein-coupled- receptor signalling networks. Nat Rev Mol Cell Biol 2004; 5:998-1012.
18. Couty JP, Gershengorn MC. Insights into the viral G protein-coupled receptor encoded by human herpesvirus type 8 (HHV-8). Biol Cell 2004; 96:349-54.
19. Sodhi A, Montaner S, Patel V, et al. The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1α. Cancer Res 2000; 60:4873-80.
20. Couty JP, Geras-Raaka E, Weksler BB, Gershengorn MC. Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor signals through multiple pathways in endothelial cells. J Biol Chem 2001; 276:33805-11.
21. Pati S, Cavrois M, Guo HG, et al. Activation of NF-kappaB by the human herpesvirus 8 chemokine receptor ORF74: Evidence for a paracrine model of Kaposi's sarcoma pathogenesis. J Virol 2001; 75:8660-73.
22. Schwarz M, Murphy PM. Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-kappa B and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant. J Immunol 2001; 167:505-13.
23. Montaner S, Sodhi A, Pece S, Mesri EA, Gutkind JS. The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B. Cancer Res 2001; 61:2641-48.
24. Pati S, Foulke Jr JS, Barabitskaya O, et al. Human herpesvirus 8-encoded vGPCR activates nuclear factor of activated T cells and collaborates with human immunodeficiency virus type 1 Tat. J Virol 2003; 77:5759-73.
25. Sodhi A, Montaner S, Patel V, et al. Akt plays a central role in sarcomagenesis induced by Kaposi's sarcoma herpesvirus-encoded G protein-coupled receptor. Proc Natl Acad Sci USA 2004; 101:4821-26.
26. Carpenter CL, Cantley LC. Phosphoinositide 3-kinase and the regulation of cell growth. Biochim Biophys Acta 1996; 1288:M11-16.
27. Downward J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 1998; 10:262-67.
28. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell 2003; 4:257-62.
29. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2:489-501.
30. Manning BD, Cantley LC. 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 2003; 31:573-78.
31. Richardson CJ, Schalm SS, Blenis J. PI3-kinase and TOR: PIKTORing cell growth. Semin Cell Dev Biol 2004; 15:147-59.
32. Garami A, Zwartkruis FJ, Nobukuni T, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell 2003; 11:1457-66.
33. 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.
34. 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.
35. Aoki M, Blazek E, Vogt PK. A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt. Proc Natl Acad Sci USA 2001; 98:136-41.
36. Gingras AC, Kennedy SG, O'Leary MA, Sonenberg N, Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev 1998; 12:502-13.
37. Majumder PK, Febbo PG, Bikoff R, et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 2004; 10:594-601.
38. Wislez M, Spencer ML, Izzo JG, et al. Inhibition of mammalian target of rapamycin reverses alveolar epithelial neoplasia induced by oncogenic K-ras. Cancer Res 2005; 65:3226-35.
39. Manning BD. Balancing Akt with S6K: Implications for both metabolic diseases and tumorigenesis. J Cell Biol 2004; 167:399-403.
40. Sodhi A, Chaisuparat R, Hu J, et al. The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Cancer Cell 2006; 10:133-43.
41. Kwiatkowski DJ, Zhang H, Bandura JL, et al. 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 2002; 11:525-34.
42. Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ. Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest 1999; 104:687-95.
43. Schwartz RA. Kaposi's sarcoma. Ann Transplant 1998; 3:5-12.
44. McCaffrey P. Sirolimus does double duty after organ transplantation. Lancet Oncol 2005; 6:261.
45. Campistol JM, Gutierrez-Dalmau A, Torregrosa JV. Conversion to sirolimus: A successful treatment for posttransplantation Kaposi's sarcoma. Transplantation 2004; 77:760-62.
46. Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005; 352:1317-23.
47. Zmonarski SC, Boratynska M, Rabczynski J, Kazimierczak K, Klinger M. Regression of Kaposi's sarcoma in renal graft recipients after conversion to sirolimus treatment. Transplant Proc 2005; 37:964-66.
48. Gutierrez-Dalmau A, Sanchez-Fructuoso A, Sanz-Guajardo A, et al. Efficacy of conversion to sirolimus in posttransplantation Kaposi's sarcoma. Transplant Proc 2005; 37:3836-3838.
49. Mohsin N, Budruddin M, Pakkyara A, et al. Complete regression of visceral Kaposi's sarcoma after conversion to sirolimus. Exp Clin Transplant 2005; 3:366-69.
50. Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 2006; 17:581-89.
51. Lebbe C, Euvrard S, Barrou B, et al. Sirolimus conversion for patients with posttransplant Kaposi's sarcoma. Am J Transplant 2006; 6:2164-68.
52. Kolhe N, Mamode N, Van der Walt J, Pattison J. Regression of post-transplant Kaposi's sarcoma using sirolimus. Int J Clin Pract 2006; 60:1509-12.
53. Sanchez-Fructuoso A, Conesa J, Perez Flores I, et al. Conversion to sirolimus in renal transplant patients with tumors. Transplant Proc 2006; 38:2451-52.
54. Penn I. Sarcomas in organ allograft recipients. Transplantation 1995; 60:1485-91.
55. Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. N Engl J Med 2005; 352:1371-73.
56. Weenink JJ, Groeneveld JO, de Fijter CW. Sirolimus monotherapy for Kaposi's sarcoma in an HIV-negative patient. Lancet Oncol 2006; 7:875-76.
57. Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin Jr WG. TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 2003; 4:147-58.
58. Humar R, Kiefer FN, Berns H, Resink TJ, Battegay EJ. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling. Faseb J 2002; 16:771-80.
59. Mayerhofer M, Valent P, Sperr WR, Griffin JD, Sillaber C. BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1α, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood 2002; 100:3767-75.
60. Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol 2002; 22:7004-14.
61. Shi Y, Yan H, Frost P, Gera J, Lichtenstein A. 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 2005; 4:1533-40.
62. O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006; 66:1500-08.
63. Harrington LS, Findlay GM, Lamb RF. Restraining PI3K: mTOR signalling goes back to the membrane. Trends Biochem Sci 2005; 30:35-42.
64. Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005; 8:179-83.
65. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307:1098-1101.
66. Hresko RC, Mueckler M. mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. J Biol Chem 2005; 280:40406-40416.
67. Sarbassov DD, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22:159-168.
68. Easton JB, Kurmasheva RT, Houghton PJ. IRS-1: Auditing the effectiveness of mTOR inhibitors. Cancer Cell 2006; 9:153-55.
69. Rosen N, She QB. AKT and cancer-is it all mTOR? Cancer Cell 2006; 10:254-56.
70. Stoeltzing O, Meric-Bernstam F, Ellis LM. Intracellular signaling in tumor and endothelial cells: The expected and, yet again, the unexpected. Cancer Cell 2006; 10:89-91.