Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells

Cancer Letters

Volumn 357, Issue 2, 2015, Pages 612-623

  Teo, Theodosia ^a   Yu, Mingfeng ^a   Yang, Yuchao ^a   Gillam, Todd ^a   Lam, Frankie ^a   Sykes, Matthew J ^a   Wang, Shudong ^a  

^a UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

Author keywords

Apoptosis; Cell cycle; CGP57380; Chronic myeloid leukemia; Mnk inhibitor; Rapamycin

Indexed keywords

CGP 57380; CYCLIN D1; INITIATION FACTOR 4E; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE INTERACTING KINASE; MNK1 4; MNKI 57; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; UNCLASSIFIED DRUG; EIF4EBP1 PROTEIN, HUMAN; ENZYME INHIBITOR; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MKNK1 PROTEIN, HUMAN; MKNK2 PROTEIN, HUMAN; MULTIPROTEIN COMPLEX; PHOSPHOPROTEIN; PROTEIN SERINE THREONINE KINASE; SIGNAL PEPTIDE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TARGET OF RAPAMYCIN KINASE; THREONINE;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CELL CYCLE PROGRESSION; CELL CYCLE S PHASE; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC MYELOID LEUKEMIA; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG STRUCTURE; G1 PHASE CELL CYCLE CHECKPOINT; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; LEUKEMIA CELL; PROTEIN DEPHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; ANTAGONISTS AND INHIBITORS; BLAST CELL CRISIS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; FLOW CYTOMETRY; GENETICS; HCT116 CELL LINE; HT 29 CELL LINE; K562 CELL LINE; MCF 7 CELL LINE; METABOLISM; PATHOLOGY; PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL LINE; U937 CELL LINE; WESTERN BLOTTING;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; APOPTOSIS; BLAST CRISIS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CYCLIN D1; DRUG SYNERGISM; ENZYME INHIBITORS; FLOW CYTOMETRY; G1 PHASE CELL CYCLE CHECKPOINTS; HCT116 CELLS; HT29 CELLS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; K562 CELLS; MCF-7 CELLS; MOLECULAR STRUCTURE; MULTIPROTEIN COMPLEXES; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; THREONINE; TOR SERINE-THREONINE KINASES; U937 CELLS;

EID: 84920757615     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2014.12.029     Document Type: Article

References (59)

1. Roccaro A.M., Sacco A., Husu E.N., Pitsillides C., Vesole S., Azab A.K., et al. Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia. Blood 2010, 115:559-569.
2. McCubrey J.A., Steelman L.S., Abrams S.L., Lee J.T., Chang F., Bertrand F.E., et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv. Enzyme Regul 2006, 46:249-279.
3. Hou J., Lam F., Proud C., Wang S. Targeting Mnks for cancer therapy. Oncotarget 2012, 3:118-131.
4. Diab S., Kumarasiri M., Yu M., Teo T., Proud C., Milne R., et al. MAP kinase-interacting kinases - emerging targets against cancer. Chem. Biol 2014, 21:441-452.
5. Scheper G.C., Morrice N.A., Kleijn M., Proud C.G. The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol. Cell. Biol 2001, 21:743-754.
6. Parra J.L., Buxade M., Proud C.G. Features of the catalytic domains and C termini of the MAPK signal-integrating kinases Mnk1 and Mnk2 determine their differing activities and regulatory properties. J. Biol. Chem 2005, 280:37623-37633.
7. Waskiewicz A.J., Flynn A., Proud C.G., Cooper J.A. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 1997, 16:1909-1920.
8. Wang X., Flynn A., Waskiewicz A.J., Webb B.L., Vries R.G., Baines I.A., et al. The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways. J. Biol. Chem 1998, 273:9373-9377.
9. Rhoads R.E. Cap recognition and the entry of mRNA into the protein synthesis initiation cycle. Trends Biochem. Sci 1988, 13:52-56.
10. Clemens M.J., Bommer U.A. Translational control: the cancer connection. Int. J. Biochem. Cell Biol 1999, 31:1-23.
11. Mamane Y., Petroulakis E., Rong L., Yoshida K., Ler L.W., Sonenberg N. eIF4E-from translation to transformation. Oncogene 2004, 23:3172-3179.
12. Hiremath L.S., Webb N.R., Rhoads R.E. Immunological detection of the messenger RNA cap-binding protein. J. Biol. Chem 1985, 260:7843-7849.
13. Duncan R., Hershey J.W. Identification and quantitation of levels of protein synthesis initiation factors in crude HeLa cell lysates by two-dimensional polyacrylamide gel electrophoresis. J. Biol. Chem 1983, 258:7228-7235.
14. Gingras A.C., Kennedy S.G., O'Leary M.A., Sonenberg N., Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev 1998, 12:502-513.
15. Wullschleger S., Loewith R., Hall M.N. TOR signaling in growth and metabolism. Cell 2006, 124:471-484.
16. Pyronnet S., Imataka H., Gingras A.C., Fukunaga R., Hunter T., Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999, 18:270-279.
17. Furic L., Rong L., Larsson O., Koumakpayi I.H., Yoshida K., Brueschke A., et al. eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:14134-14139.
18. Ueda T., Sasaki M., Elia A.J., Chio I.I.C., Hamada K., Fukunaga R., et al. Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:13984-13990.
19. Ueda T., Watanabe-Fukunaga R., Fukuyama H., Nagata S., Fukunaga R. Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or development. Mol. Cell. Biol 2004, 24:6539-6549.
20. Bain J., Plater L., Elliott M., Shpiro N., Hastie C.J., McLauchlan H., et al. The selectivity of protein kinase inhibitors: a further update. Biochem. J. 2007, 408:297-315.
21. Konicek B.W., Stephens J.R., McNulty A.M., Robichaud N., Peery R.B., Dumstorf C.A., et al. Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases. Cancer Res 2011, 71:1849-1857.
22. Wheater M.J., Johnson P.W., Blaydes J.P. The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival. Cancer Biol. Ther 2010, 10:728-735.
23. Zhang M., Fu W., Prabhu S., Moore J.C., Ko J., Kim J.W., et al. Inhibition of polysome assembly enhances imatinib activity against chronic myelogenous leukemia and overcomes imatinib resistance. Mol. Cell. Biol 2008, 28:6496-6509.
24. Altman J.K., Szilard A., Konicek B.W., Iversen P.W., Kroczynska B., Glaser H., et al. Inhibition of Mnk kinase activity by cercosporamide and suppressive effects on acute myeloid leukemia precursors. Blood 2013, 121:3675-3681.
25. Wendel H.G., Silva R.L.A., Malina A., Mills J.R., Zhu H., Ueda T., et al. Dissecting eIF4E action in tumorigenesis. Genes Dev 2007, 21:3232-3237.
26. Grzmil M., Huber R.M., Hess D., Frank S., Hynx D., Moncayo G., et al. MNK1 pathway activity maintains protein synthesis in rapalog-treated gliomas. J. Clin. Invest 2014, 124:742-754.
27. Diab S., Teo T., Kumarasiri M., Li P., Yu M., Lam F., et al. Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as potent Mnk2 inhibitors: synthesis, SAR analysis and biological evaluation. ChemMedChem 2014, 9:962-972.
28. Chrestensen C.A., Shuman J.K., Eschenroeder A., Worthington M., Gram H., Sturgill T.W. MNK1 and MNK2 regulation in HER2-overexpressing breast cancer lines. J. Biol. Chem 2007, 282:4243-4252.
29. Satheesha S., Cookson V.J., Coleman L.J., Ingram N., Madhok B., Hanby A.M., et al. Response to mTOR inhibition: activity of eIF4E predicts sensitivity in cell lines and acquired changes in eIF4E regulation in breast cancer. Mol. Cancer 2011, 10:19.
30. Noh W.C., Mondesire W.H., Peng J., Jian W., Zhang H., Dong J., et al. Determinants of rapamycin sensitivity in breast cancer cells. Clin. Cancer Res 2004, 10:1013-1023.
31. Altman J.K., Glaser H., Sassano A., Joshi S., Ueda T., Watanabe-Fukunaga R., et al. Negative regulatory effects of Mnk kinases in the generation of chemotherapy-induced antileukemic responses. Mol. Pharmacol 2010, 78:778-784.
32. Bianchini A., Loiarro M., Bielli P., Busà R., Paronetto M.P., Loreni F., et al. Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis 2008, 29:2279-2288.
33. Marzec M., Liu X., Wysocka M., Rook A.H., Odum N., Wasik M.A. Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells. PLoS ONE 2011, 6:e24849.
34. Adesso L., Calabretta S., Barbagallo F., Capurso G., Pilozzi E., Geremia R., et al. Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway. Oncogene 2013, 32:2848-2857.
35. Sun S.Y., Rosenberg L.M., Wang X., Zhou Z., Yue P., Fu H., et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005, 65:7052-7058.
36. Wang S., Wood G., Meades C., Griffiths G., Midgley C., McNae I., et al. Synthesis and biological activity of 2-anilino-4-(1H-pyrrol-3-yl) pyrimidine CDK inhibitors. Bioorg. Med. Chem. Lett 2004, 14:4237-4240.
37. Lam F., Abbas A.Y., Shao H., Teo T., Adams J., Li P., et al. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget 2014, 5:7691-7704.
38. Tellmann G. The E-method: a highly accurate technique for gene-expression analysis. Nat. Methods 2006, 3:i-ii.
39. Lim S., Saw T.Y., Zhang M., Janes M.R., Nacro K., Hill J., et al. Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:E2298-E2307.
40. Cheng Z.Y., Guo X.L., Yang X.Y., Niu Z.Y., Li S.H., Wang S.Y., et al. PTEN and rapamycin inhibiting the growth of K562 cells through regulating mTOR signaling pathway. J. Exp. Clin. Cancer Res 2008, 27:87.
41. Dahia P.L., Aguiar R.C., Alberta J., Kum J.B., Caron S., Sill H., et al. PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanisms in haematological malignancies. Hum. Mol. Genet 1999, 8:185-193.
42. Fu C.T., et al. An evolutionarily conserved PTEN-C/EBPalpha-CTNNA1 axis controls myeloid development and transformation. Blood 2010, 115:4715-4724.
43. Gao X., Zhang Y., Arrazola P., Hino O., Kobayashi T., Yeung R.S., et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat. Cell Biol 2002, 4:699-704.
44. Grzmil M., Morin P., Lino M.M., Merlo A., Frank S., Wang Y., et al. MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-beta signaling pathway in human glioblastoma. Cancer Res 2011, 71:2392-2402.
45. Wang X., Beugnet A., Murakami M., Yamanaka S., Proud C.G. 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, 25:2558-2572.
46. Eckerdt F., Beauchamp E., Bell J., Iqbal A., Su B., Fukunaga R., et al. Regulatory effects of a Mnk2-eIF4E feedback loop during mTORC1 targeting of human medulloblastoma cells. Oncotarget 2014, 5:8442-8451.
47. Wang X., Yue P., Chan C.B., Ye K., Ueda T., Watanabe-Fukunaga R., et al. Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation. Mol. Cell. Biol 2007, 27:7405-7413.
48. Averous J., Fonseca B.D., Proud C.G. Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene 2008, 27:1106-1113.
49. Müller D., Lasfargues C., El Khawand S., Alard A., Schneider R.J., Bousquet C., et al. 4E-BP restrains eIF4E phosphorylation. Translation 2013, 1:e25819.
50. Gingras A.C., Raught B., Gygi S.P., Niedzwiecka A., Miron M., Burley S.K., et al. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev 2001, 15:2852-2864.
51. Proud C.G. Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem. J. 2007, 403:217-234.
52. Neganova I., Lako M. G1 to S phase cell cycle transition in somatic and embryonic stem cells. J. Anat 2008, 213:30-44.
53. Pause A., Belsham G.J., Gingras A.C., Donze O., Lin T.A., Lawrence J.C., et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature 1994, 371:762-767.
54. Stead R.L., Proud C.G. Rapamycin enhances eIF4E phosphorylation by activating MAP kinase-interacting kinase 2a (Mnk2a). FEBS Lett 2013, 587:2623-2628.
55. She Q.B., Halilovic E., Ye Q., Zhen W., Shirasawa S., Sasazuki T., et al. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 2010, 18:39-51.
56. Graff J.R., Konicek B.W., Carter J.H., Marcusson E.G. Targeting the eukaryotic translation initiation factor 4E for cancer therapy. Cancer Res 2008, 68:631-634.
57. Soria J.C., Blay J.Y., Spano J.P., Pivot X., Coscas Y., Khayat D. Added value of molecular targeted agents in oncology. Ann. Oncol 2011, 22:1703-1716.
58. Engelman J.A., et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med 2008, 14:1351-1356.
59. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.