Regulation of mTOR complex 2 signaling in neurofibromatosis 2-deficient target cell types

Molecular Cancer Research

Volumn 10, Issue 5, 2012, Pages 649-659

  James, Marianne F ^a   Stivison, Elizabeth ^a   Beauchamp, Roberta ^a   Han, Sangyeul ^a   Li, Hua ^b   Wallace, Margaret R ^b   Gusella, James F ^a   Stemmer Rachamimov, Anat O ^a   Ramesh, Vijaya ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MERLIN; PROTEIN KINASE B; RAPAMYCIN; TUBERIN;

ARACHNOID; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; HUMAN TISSUE; MENINGIOMA; NEURILEMOMA; NEUROFIBROMATOSIS; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN PHOSPHORYLATION; RNA INTERFERENCE; SCHWANN CELL; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR GENE;

CELL LINE, TUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MENINGEAL NEOPLASMS; MENINGIOMA; NAPHTHYRIDINES; NEURILEMMOMA; NEUROFIBROMIN 2; ONCOGENE PROTEIN V-AKT; PROTEINS; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SIROLIMUS; TRANSCRIPTION FACTORS; TUBEROUS SCLEROSIS;

EID: 84861180854     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-11-0425-T     Document Type: Article

References (50)

1. Evans DG. Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med 2009;11:599-610.
2. Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 1993;72: 791-800. (Pubitemid 23093886)
3. Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2. Nature 1993;363: 515-21. (Pubitemid 23186636)
4. Fehon RG, McClatchey AI, Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol 2010;11:276-87.
5. Lallemand D, Manent J, Couvelard A, Watillilaux A, Siena M, Chareyre F, et al. Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas. Oncogene 2009;28: 854-65.
6. McClatchey AI, Fehon RG. Merlin and the ERM proteins-regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol 2009;19:198-206.
7. Kaempchen K, Mielke K, Utermark T, Langmesser S, Hanemann CO. Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells. Hum Mol Genet 2003;12:1211-21. (Pubitemid 36722601)
8. Rong R, Tang X, Gutmann DH, Ye K. Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L. Proc Natl Acad Sci U S A 2004;101:18200-5. (Pubitemid 40054097)
9. Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, et al. The tumour-suppressor genes NF2/Merlin and expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol 2006;8:27-36. (Pubitemid 43064794)
10. Morrison H, Sperka T, Manent J, Giovannini M, Ponta H, Herrlich P. Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Res 2007;67:520-7. (Pubitemid 46192188)
11. Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 2007;21:2747-61. (Pubitemid 350070721)
12. Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila JL, Christian N, et al. A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell 2011;19:527-40.
13. Li W, Giancotti FG. Merlin's tumor suppression linked to inhibition of the E3 ubiquitin ligase CRL4 (DCAF1). Cell Cycle 2010;9:4433-6.
14. James MF, Han S, Polizzano C, Plotkin SR, Manning BD, Stemmer-Rachamimov AO, et al. NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol 2009;29: 4250-61.
15. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007;12:9-22. (Pubitemid 47001784)
16. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 2009;10:307-18.
17. Huang J, Dibble CC, Matsuzaki M, Manning BD. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol 2008;28:4104-15. (Pubitemid 351812994)
18. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006;22:159-68.
19. Pearce LR, Komander D, Alessi DR. The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol 2010;11:9-22.
20. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals thatmTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 2006;11:859-71. (Pubitemid 44804279)
21. Garcia-Martinez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J 2008;416: 375-85.
22. Shah OJ, Hunter T. Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol 2006;26: 6425-34. (Pubitemid 44277883)
23. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 2004;166:213-23. (Pubitemid 38988774)
24. Zhang H, Bajraszewski N, Wu E, Wang H, Moseman AP, Dabora SL, et al. PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. J Clin Invest 2007;117:730-8. (Pubitemid 46348531)
25. Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villen J, et al. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 2011;332: 1322-6.
26. Hsu PP, Kang SA, Rameseder J, Zhang Y, Attina KA, Lim D, et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 2011;332:1317-22.
27. Huang J, Wu S, Wu CL, Manning BD. Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors. Cancer Res 2009;69:6107-14.
28. Efeyan A, Sabatini DM. mTOR and cancer: many loops in one pathway. Curr Opin Cell Biol 2010;22:169-76.
29. James MF, Lelke JM, Maccollin M, Plotkin SR, Stemmer-Rachamimov AO, Ramesh V, et al. Modeling NF2 with human arachnoidal and meningioma cell culture systems: NF2 silencing reflects the benign character of tumor growth. Neurobiol Dis 2008;29:278-92.
30. Fishbein L, Zhang X, Fisher LB, Li H, Campbell-Thompson M, Yachnis A, et al. In vitro studies of steroid hormones in neurofibromatosis 1 tumors and Schwann cells. Mol Carcinog 2007;46: 512-23. (Pubitemid 47068070)
31. Li H, Chang L-J, Muir D, Wallace MR. Immortalization of normal and NF1 neurofibroma-derived Schwann cell cultures. Manuscript in preparation.
32. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307:1098-101. (Pubitemid 40262113)
33. Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008;412:179-90. (Pubitemid 351758225)
34. Lopez-Lago MA, Okada T, Murillo MM, Socci N, Giancotti FG. Loss of the tumor suppressor gene NF2, encoding merlin, constitutively activates integrin-dependent mTORC1 signaling. Mol Cell Biol 2009;29: 4235-49.
35. Fraenzer JT, Pan H, Minimo L Jr., Smith GM, Knauer D, Hung G. Overexpression of the NF2 gene inhibits schwannomacell proliferation through promoting PDGFR degradation. Int J Oncol 2003;23:1493-500.
36. Ammoun S, Flaiz C, Ristic N, Schuldt J, Hanemann CO. Dissecting and targeting the growth factor-dependent and growth factor-independent extracellular signal-regulated kinase pathway in human schwannoma. Cancer Res 2008;68:5236-45.
37. AmmounS, Cunliffe CH, Allen JC, Chiriboga L, Giancotti FG, Zagzag D, et al. ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma. Neuro Oncol 2010;12:834-43.
38. Jacob A, Lee TX, Neff BA, Miller S, Welling B, Chang LS. Phosphatidylinositol 3-kinase/AKT pathway activation in human vestibular schwannoma. Otol Neurotol 2008;29:58-68.
39. Hilton DA, Ristic N, Hanemann CO. Activation of ERK, AKT and JNK signalling pathways in human schwannomas in situ. Histopathology 2009;55:744-9.
40. 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 SciUS A2008;105:17414-9.
41. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009;284:8023-32.
42. Donev IS, Wang W, Yamada T, Li Q, Takeuchi S, Matsumotot K, et al. Transient PI3K inhibition induces apoptosis and overcomes HGF-mediated resistance to EGFR-TKIs in EGFR mutant lung cancer. Clin Cancer Res 2011;17:2260-9.
43. Huang J, Manning BD. A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans 2009;37:217-22.
44. Dibble CC, Asara JM, Manning BD. Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol 2009;29:5657-70.
45. Julien LA, Carriere A, Moreau J, Roux PP. mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol 2010;30:908-21.
46. Pearce LR, Sommer EM, Sakamoto K, Wullschleger S, Alessi DR. Protor-1 is required for efficient mTORC2-mediated activation ofSGK1 in the kidney. Biochem J 2011;436:169-79.
47. Goutagny S, Yang HW, Zucman-Rossi J, Chan J, Dreyfuss JM, Park PJ, et al. Genomic profiling reveals alternative genetic pathways of meningioma malignant progression dependent on the underlying NF2 status. Clin Cancer Res 2010;16:4155-64.
48. Tyburczy ME, Kotulska K, Pokarowski P, Mieczkowski J, Kucharska J, Grajkowska W, et al. Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications. Am J Pathol 2010;176: 1878-90.
49. Campen CJ, Porter BE. Subependymal giant cell astrocytoma (SEGA) treatment update. Curr Treat Options Neurol 2011;13:380-5.
50. Wander SA, Hennessy BT, Slingerland JM. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J Clin Invest 2011;121:1231-41.