The role of mitogen- and stress-activated protein kinase pathways in melanoma

Pigment Cell and Melanoma Research

Volumn 24, Issue 5, 2011, Pages 902-921

  Lopez Bergami, Pablo ^a  

^a Facultad de Ciencias Naturales e Instituto M Lillo   (Argentina)

Author keywords

Melanoma biology; Mitogen activated protein kinase pathways; Molecular signaling events

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; A RAF KINASE; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; B RAF KINASE; B RAF KINASE INHIBITOR; CYCLIN D1; DACARBAZINE; INTERLEUKIN 1BETA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 10; MITOGEN ACTIVATED PROTEIN KINASE 11; MITOGEN ACTIVATED PROTEIN KINASE 12; MITOGEN ACTIVATED PROTEIN KINASE 13; MITOGEN ACTIVATED PROTEIN KINASE 14; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE 9; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE P38; RAF PROTEIN; SORAFENIB; STRESS ACTIVATED PROTEIN KINASE; STRESS ACTIVATED PROTEIN KINASE 1; STRESS ACTIVATED PROTEIN KINASE INHIBITOR; TUMOR NECROSIS FACTOR ALPHA; VEMURAFENIB;

CANCER GROWTH; CANCER RESISTANCE; CANCER THERAPY; CARCINOGENESIS; CELL FUNCTION; DRUG DOSE ESCALATION; ENZYME ACTIVATION; GENE IDENTIFICATION; GENE MUTATION; HUMAN; MELANOMA; MELANOMAGENESIS; NONHUMAN; ONCOGENE; OVERALL SURVIVAL; PROGRESSION FREE SURVIVAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

HUMANS; MAP KINASE SIGNALING SYSTEM; MELANOMA; MITOGEN-ACTIVATED PROTEIN KINASES; STRESS, PHYSIOLOGICAL;

EID: 80053898449     PISSN: 17551471     EISSN: 1755148X     Source Type: Journal    
DOI: 10.1111/j.1755-148X.2011.00908.x     Document Type: Review

References (231)

1. Abbas, S., Bhoumik, A., Dahl, R., Vasile, S., Krajewski, S., Cosford, N.D., and Ronai, Z.A. (2007). Preclinical studies of celastrol and acetyl isogambogic acid in melanoma. Clin. Cancer Res. 13, 6769-6778.
2. Abdel-Malek, Z., Swope, V.B., Suzuki, I., Akcali, C., Harriger, M.D., Boyce, S.T., Urabe, K., and Hearing, V.J. (1995). Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. Proc. Natl. Acad. Sci. U S A 92, 1789-1793.
3. Adjei, A.A. (2001). Blocking oncogenic Ras signaling for cancer therapy. J. Natl Cancer Inst. 93, 1062-1074.
4. Aguirre Ghiso, J.A., Kovalski, K., and Ossowski, L. (1999). Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J. Cell Biol. 147, 89-104.
5. Aguirre-Ghiso, J.A., Estrada, Y., Liu, D., and Ossowski, L. (2003). ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res. 63, 1684-1695.
6. Ahmed, S.U., and Milner, J. (2009). Basal cancer cell survival involves JNK2 suppression of a novel JNK1/c-Jun/Bcl-3 apoptotic network. PLoS ONE 4, e7305.
7. Ahn, J.H., Jin, S.H., and Kang, H.Y. (2008). LPS induces melanogenesis through p38 MAPK activation in human melanocytes. Arch. Dermatol. Res. 300, 325-329.
8. Alexaki, V.I., Javelaud, D., and Mauviel, A. (2008). JNK supports survival in melanoma cells by controlling cell cycle arrest and apoptosis. Pigment Cell Melanoma Res. 21, 429-438.
9. An, W.W., Wang, M.W., Tashiro, S., Onodera, S., and Ikejima, T. (2005). Mitogen-activated protein kinase-dependent apoptosis in norcan-tharidin-treated A375-S2 cells is proceeded by the activation of protein kinase C. Chin. Med. J. (Engl.) 118, 198-203.
10. Angel, P., Imagawa, M., Chiu, R., Stein, B., Imbra, R.J., Rahmsdorf, H.J., Jonat, C., Herrlich, P., and Karin, M. (1987). Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49, 729-739.
11. Arozarena, I., Sanchez-Laorden, B., Packer, L., Hidalgo-Carcedo, C., Hayward, R., Viros, A., Sahai, E., and Marais, R. (2011). Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cancer Cell 19, 45-57.
12. Ashwell, J.D. (2006). The many paths to p38 mitogen-activated protein kinase activation in the immune system. Nat. Rev. Immunol. 6, 532-540.
13. Bansal, R., and Nikiforov, M.A. (2010). Pathways of oncogene-induced senescence in human melanocytic cells. Cell Cycle 9, 2782-2788.
14. Behrens, A., Jochum, W., Sibilia, M., and Wagner, E.F. (2000). Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene 19, 2657-2663.
15. Bellei, B., Maresca, V., Flori, E., Pitisci, A., Larue, L., and Picardo, M. (2010). p38 regulates pigmentation via proteasomal degradation of tyrosinase. J. Biol. Chem. 285, 7288-7299.
16. Bhatt, K.V., Spofford, L.S., Aram, G., Mcmullen, M., Pumiglia, K., and Aplin, A.E. (2005). Adhesion control of cyclin D1 and p27Kip1 levels is deregulated in melanoma cells through BRAF-MEK-ERK signaling. Oncogene 24, 3459-3471.
17. Bhatt, K.V., Hu, R., Spofford, L.S., and Aplin, A.E. (2007). Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Oncogene 26, 1056-1066.
18. Bogoyevitch, M.A., and Kobe, B. (2006). Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases. Microbiol. Mol. Biol. Rev. 70, 1061-1095.
19. Bollag, G., Hirth, P., Tsai, J. et al. (2010). Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467, 596-599.
20. Boukerche, H., Su, Z.Z., Emdad, L., Sarkar, D., and Fisher, P.B. (2007). mda-9/Syntenin regulates the metastatic phenotype in human melanoma cells by activating nuclear factor-kappaB. Cancer Res. 67, 1812-1822.
21. Boukerche, H., Su, Z.Z., Prevot, C., Sarkar, D., and Fisher, P.B. (2008). mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src. Proc. Natl. Acad. Sci. U S A 105, 15914-15919.
22. Boukerche, H., Aissaoui, H., Prevost, C., Hirbec, H., Das, S.K., Su, Z.Z., Sarkar, D., and Fisher, P.B. (2010). Src kinase activation is mandatory for MDA-9/syntenin-mediated activation of nuclear factor-kappaB. Oncogene 29, 3054-3066.
23. Boutros, T., Chevet, E., and Metrakos, P. (2008). Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer. Pharmacol. Rev. 60, 261-310.
24. Bradham, C., and McClay, D.R. (2006). p38 MAPK in development and cancer. Cell Cycle 5, 824-828.
25. Brancho, D., Tanaka, N., Jaeschke, A., Ventura, J.J., Kelkar, N., Tanaka, Y., Kyuuma, M., Takeshita, T., Flavell, R.A., and Davis, R.J. (2003). Mechanism of p38 MAP kinase activation in vivo. Genes Dev. 17, 1969-1978.
26. Brondello, J.M., Pouyssegur, J., and Mckenzie, F.R. (1999). Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. Science 286, 2514-2517.
27. Bulavin, D.V., and Fornace Jr, A.J. (2004). p38 MAP kinase's emerging role as a tumor suppressor. Adv. Cancer Res. 92, 95-118.
28. Bulavin, D.V., Demidov, O.N., Saito, S. et al. (2002). Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat. Genet. 31, 210-215.
29. Cagnol, S., and Chambard, J.C. (2010). ERK and cell death: mechanisms of ERK-induced cell death - apoptosis, autophagy and senescence. FEBS J. 277, 2-21.
30. Cargnello, M., and Roux, P.P. (2011). Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol. Mol. Biol. Rev. 75, 50-83.
31. Carreira, S., Goodall, J., Aksan, I., La Rocca, S.A., Galibert, M.D., Denat, L., Larue, L., and Goding, C.R. (2005). Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression. Nature 433, 764-769.
32. Chapman, P.B., Hauschild, A., Robert, C. et al. (2011). Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507-2516.
33. Choi, B.Y., Choi, H.S., Ko, K., Cho, Y.Y., Zhu, F., Kang, B.S., Ermakova, S.P., Ma, W.Y., Bode, A.M., and Dong, Z. (2005). The tumor suppressor p16(INK4a) prevents cell transformation through inhibition of c-Jun phosphorylation and AP-1 activity. Nat. Struct. Mol. Biol. 12, 699-707.
34. Collisson, E.A., De, A., Suzuki, H., Gambhir, S.S., and Kolodney, M.S. (2003). Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade. Cancer Res. 63, 5669-5673.
35. Cook, A.L., and Sturm, R.A. (2008). POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis. Pigment Cell Melanoma Res. 21, 611-626.
36. Corcoran, R.B., Dias-Santagata, D., Bergethon, K., Iafrate, A.J., Settleman, J., and Engelman, J.A. (2010). BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci. Signal. 3, ra84.
37. Corre, S., Primot, A., Sviderskaya, E., Bennett, D.C., Vaulont, S., Goding, C.R., and Galibert, M.D. (2004). UV-induced expression of key component of the tanning process, the POMC and MC1R genes, is dependent on the p-38-activated upstream stimulating factor-1 (USF-1). J. Biol. Chem. 279, 51226-51233.
38. Cronin, J.C., Wunderlich, J., Loftus, S.K. et al. (2009). Frequent mutations in the MITF pathway in melanoma. Pigment Cell Melanoma Res. 22, 435-444.
39. Cuadrado, A., and Nebreda, A.R. (2010). Mechanisms and functions of p38 MAPK signalling. Biochem. J. 429, 403-417.
40. Cuenda, A., and Rousseau, S. (2007). p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim. Biophys. Acta 1773, 1358-1375.
41. Curtin, J.A., Busam, K., Pinkel, D., and Bastian, B.C. (2006). Somatic activation of KIT in distinct subtypes of melanoma. J. Clin. Oncol. 24, 4340-4346.
42. Dankort, D., Filenova, E., Collado, M., Serrano, M., Jones, K., and Mcmahon, M. (2007). A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev. 21, 379-384.
43. Davies, H., Bignell, G.R., Cox, C. et al. (2002). Mutations of the BRAF gene in human cancer. Nature 417, 949-954.
44. Davis, R.J. (2000). Signal transduction by the JNK group of MAP kinases. Cell 103, 239-252.
45. Delmas, V., Beermann, F., Martinozzi, S. et al. (2007). Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev. 21, 2923-2935.
46. Denkert, C., Siegert, A., Leclere, A., Turzynski, A., and Hauptmann, S. (2002). An inhibitor of stress-activated MAP-kinases reduces invasion and MMP-2 expression of malignant melanoma cells. Clin. Exp. Metastasis 19, 79-85.
47. Denoyelle, C., Abou-Rjaily, G., Bezrookove, V. et al. (2006). Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway. Nat. Cell Biol. 8, 1053-1063.
48. Dhawan, P., and Richmond, A. (2002). A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells. J. Biol. Chem. 277, 7920-7928.
49. Dhomen, N., Reis-Filho, J.S., Da Rocha Dias, S., Hayward, R., Savage, K., Delmas, V., Larue, L., Pritchard, C., and Marais, R. (2009). Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell 15, 294-303.
50. Ding, X.Z., and Adrian, T.E. (2001). MEK/ERK-mediated proliferation is negatively regulated by P38 map kinase in the human pancreatic cancer cell line, PANC-1. Biochem. Biophys. Res. Commun. 282, 447-453.
51. Djerf, E.A., Trinks, C., Abdiu, A., Thunell, L.K., Hallbeck, A.L., and Walz, T.M. (2009). ErbB receptor tyrosine kinases contribute to proliferation of malignant melanoma cells: inhibition by gefitinib (ZD1839). Melanoma Res. 19, 156-166.
52. Dolado, I., Swat, A., Ajenjo, N., De Vita, G., Cuadrado, A., and Nebreda, A.R. (2007). p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis. Cancer Cell 11, 191-205.
53. Du, L., Lyle, C.S., Obey, T.B., Gaarde, W.A., Muir, J.A., Bennett, B.L., and Chambers, T.C. (2004). Inhibition of cell proliferation and cell cycle progression by specific inhibition of basal JNK activity: evidence that mitotic Bcl-2 phosphorylation is JNK-independent. J. Biol. Chem. 279, 11957-11966.
54. Eferl, R., Ricci, R., Kenner, L., Zenz, R., David, J.P., Rath, M., and Wagner, E.F. (2003). Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 112, 181-192.
55. Eisenmann, K.M., VanBrocklin, M.W., Staffend, N.A., Kitchen, S.M., and Koo, H.M. (2003). Mitogen-activated protein kinase pathway-dependent tumor-specific survival signaling in melanoma cells through inactivation of the proapoptotic protein bad. Cancer Res. 63, 8330-8337.
56. van Elsas, A., Zerp, S., van der Flier, S., Kruse-Wolters, M., Vacca, A., Ruiter, D.J., and Schrier, P. (1995). Analysis of N-ras mutations in human cutaneous melanoma: tumor heterogeneity detected by polymerase chain reaction/single-stranded conformation polymorphism analysis. Recent Results Cancer Res. 139, 57-67.
57. Emery, C.M., Vijayendran, K.G., Zipser, M.C. et al. (2009). MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc. Natl. Acad. Sci. U S A 106, 20411-20416.
58. Engelman, J.A. (2009). Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550-562.
59. Estrada, Y., Dong, J., and Ossowski, L. (2009). Positive crosstalk between ERK and p38 in melanoma stimulates migration and in vivo proliferation. Pigment Cell Melanoma Res. 22, 66-76.
60. Ferreiro, I., Joaquin, M., Islam, A. et al. (2010). Whole genome analysis of p38 SAPK-mediated gene expression upon stress. BMC Genomics 11, 144.
61. Ferrell Jr, J.E. (1996). Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends Biochem. Sci. 21, 460-466.
62. Flaherty, K.T., Puzanov, I., Kim, K.B. et al. (2010). Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809-819.
63. Fontijn, D., Bosch, L.J., Duyndam, M.C., Van Berkel, M.P., Janmaat, M.L., and Boven, E. (2009). Basic fibroblast growth factor-mediated overexpression of vascular endothelial growth factor in 1F6 human melanoma cells is regulated by activation of PI-3K and p38 MAPK. Cell Oncol. 31, 179-190.
64. Friedlander, P., and Hodi, F.S. (2010). Advances in targeted therapy for melanoma. Clin. Adv. Hematol. Oncol. 8, 619-627.
65. Fuchs, S.Y., Fried, V.A., and Ronai, Z. (1998). Stress-activated kinases regulate protein stability. Oncogene 17, 1483-1490.
66. Gao, Y.J., Cheng, J.K., Zeng, Q., Xu, Z.Z., Decosterd, I., Xu, X., and Ji, R.R. (2009). Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model. Exp. Neurol. 219, 146-155.
67. Garcia, M.C., Ray, D.M., Lackford, B., Rubino, M., Olden, K., and Roberts, J.D. (2009). Arachidonic acid stimulates cell adhesion through a novel p38 MAPK-RhoA signaling pathway that involves heat shock protein 27. J. Biol. Chem. 284, 20936-20945.
68. Garraway, L.A., Widlund, H.R., Rubin, M.A. et al. (2005). Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436, 117-122.
69. Genersch, E., Hayess, K., Neuenfeld, Y., and Haller, H. (2000). Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways. J. Cell Sci. 113(Pt 23), 4319-4330.
70. Giuliano, S., Ohanna, M., Ballotti, R., and Bertolotto, C. (2011). Advances in melanoma senescence and potential clinical application. Pigment Cell Melanoma Res. 24, 295-308.
71. Goel, V.K., Ibrahim, N., Jiang, G., Singhal, M., Fee, S., Flotte, T., Westmoreland, S., Haluska, F.S., Hinds, P.W., and Haluska, F.G. (2009). Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice. Oncogene 28, 2289-2298.
72. Gollob, J.A., Sciambi, C.J., Huang, Z., and Dressman, H.K. (2005). Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. Cancer Res. 65, 8869-8877.
73. Goodall, J., Wellbrock, C., Dexter, T.J., Roberts, K., Marais, R., and Goding, C.R. (2004). The Brn-2 transcription factor links activated BRAF to melanoma proliferation. Mol. Cell. Biol. 24, 2923-2931.
74. Gorden, A., Osman, I., Gai, W., He, D., Huang, W., Davidson, A., Houghton, A.N., Busam, K., and Polsky, D. (2003). Analysis of BRAF and N-RAS mutations in metastatic melanoma tissues. Cancer Res. 63, 3955-3957.
75. Grafstrom, E., Egyhazi, S., Ringborg, U., Hansson, J., and Platz, A. (2005). Biallelic deletions in INK4 in cutaneous melanoma are common and associated with decreased survival. Clin. Cancer Res. 11, 2991-2997.
76. Gray-Schopfer, V.C., Da Rocha Dias, S., and Marais, R. (2005). The role of B-RAF in melanoma. Cancer Metastasis Rev. 24, 165-183.
77. Gray-Schopfer, V., Wellbrock, C., and Marais, R. (2007). Melanoma biology and new targeted therapy. Nature 445, 851-857.
78. Greenman, C., Stephens, P., Smith, R. et al. (2007). Patterns of somatic mutation in human cancer genomes. Nature 446, 153-158.
79. Growney, J.D., Clark, J.J., Adelsperger, J., Stone, R., Fabbro, D., Griffin, J.D., and Gilliland, D.G. (2005). Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412. Blood 106, 721-724.
80. Gurzov, E.N., Bakiri, L., Alfaro, J.M., Wagner, E.F., and Izquierdo, M. (2008). Targeting c-Jun and JunB proteins as potential anticancer cell therapy. Oncogene 27, 641-652.
81. Gutkind, J.S. (2000). Regulation of mitogen-activated protein kinase signaling networks by G protein-coupled receptors. Sci. STKE 2000, re1.
82. Halaban, R., Zhang, W., Bacchiocchi, A., Cheng, E., Parisi, F., Ariyan, S., Krauthammer, M., Mccusker, J.P., Kluger, Y., and Sznol, M. (2010). PLX4032, a selective BRAF (V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 23, 190-200.
83. Han, J., and Sun, P. (2007). The pathways to tumor suppression via route p38. Trends Biochem. Sci. 32, 364-371.
84. Han, M.J., Wang, H., Beer, L.A., Tang, H.Y., Herlyn, M., and Speicher, D.W. (2010). A systems biology analysis of metastatic melanoma using in-depth three-dimensional protein profiling. Proteomics 10, 4450-4462.
85. Hassan, M., Alaoui, A., Feyen, O., Mirmohammadsadegh, A., Essmann, F., Tannapfel, A., Gulbins, E., Schulze-Osthoff, K., and Hengge, U.R. (2008). The BH3-only member Noxa causes apoptosis in melanoma cells by multiple pathways. Oncogene 27, 4557-4568.
86. Hattori, T., Hayashi, H., Chiba, T., and Onozaki, K. (2001). Activation of two distinct anti-proliferative pathways, apoptosis and p38 MAP kinase-dependent cell cycle arrest, by tumor necrosis factor in human melanoma cell line A375. Eur. Cytokine Netw. 12, 244-252.
87. Heath, E.M., Kaufman, K.L., and Christopherson, R.I. (2011). B-RAF: a contributor to the melanoma phenotype. Int. J. Biochem. Cell Biol. 43, 29-32.
88. Hoeflich, K.P., Gray, D.C., Eby, M.T. et al. (2006). Oncogenic BRAF is required for tumor growth and maintenance in melanoma models. Cancer Res. 66, 999-1006.
89. Hong, I.K., Kim, Y.M., Jeoung, D.I., Kim, K.C., and Lee, H. (2005). Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells. Exp. Mol. Med. 37, 230-239.
90. Hu, W.P., Tsai, F.Y., Yu, H.S., Sung, P.J., Chang, L.S., and Wang, J.J. (2008). Induction of apoptosis by DC-81-indole conjugate agent through NF-kappaB and JNK/AP-1 pathway. Chem. Res. Toxicol. 21, 1330-1336.
91. Huang, C.Y., and Ferrell Jr, J.E. (1996). Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. U S A 93, 10078-10083.
92. Huangfu, W.C., Qian, J., Liu, C., Liu, J., Lokshin, A.E., Baker, D.P., Rui, H., and Fuchs, S.Y. (2011). Inflammatory signaling compromises cell responses to interferon alpha. Oncogene doi:.
93. Itoh, S., Hattori, T., Hayashi, H. et al. (1999). Antiproliferative effect of IL-1 is mediated by p38 mitogen-activated protein kinase in human melanoma cell A375. J. Immunol. 162, 7434-7440.
94. Ivanov, V.N., Kehrl, J.H., and Ronai, Z. (2000). Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis. Oncogene 19, 933-942.
95. Ivanov, V.N., Fodstad, O., and Ronai, Z. (2001). Expression of ring finger-deleted TRAF2 sensitizes metastatic melanoma cells to apoptosis via up-regulation of p38, TNFalpha and suppression of NF-kappaB activities. Oncogene 20, 2243-2253.
96. Iyoda, K., Sasaki, Y., Horimoto, M. et al. (2003). Involvement of the p38 mitogen-activated protein kinase cascade in hepatocellular carcinoma. Cancer 97, 3017-3026.
97. Jaeschke, A., Karasarides, M., Ventura, J.J., Ehrhardt, A., Zhang, C., Flavell, R.A., Shokat, K.M., and Davis, R.J. (2006). JNK2 is a positive regulator of the cJun transcription factor. Mol. Cell 23, 899-911.
98. Johannessen, C.M., Boehm, J.S., Kim, S.Y. et al. (2010). COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468, 968-972.
99. Johansson, P., Pavey, S., and Hayward, N. (2007). Confirmation of a BRAF mutation-associated gene expression signature in melanoma. Pigment Cell Res. 20, 216-221.
100. Jones, S., Zhang, X., Parsons, D.W. et al. (2008). Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801-1806.
101. Jorgensen, K., Davidson, B., and Florenes, V.A. (2006). Activation of c-jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma. Mod. Pathol. 19, 1446-1455.
102. Jovanovic, B., Krockel, D., Linden, D., Nilsson, B., Egyhazi, S., and Hansson, J. (2008). Lack of cytoplasmic ERK activation is an independent adverse prognostic factor in primary cutaneous melanoma. J. Invest. Dermatol. 128, 2696-2704.
103. Junttila, M.R., Ala-Aho, R., Jokilehto, T., Peltonen, J., Kallajoki, M., Grenman, R., Jaakkola, P., Westermarck, J., and Kahari, V.M. (2007). p38alpha and p38delta mitogen-activated protein kinase isoforms regulate invasion and growth of head and neck squamous carcinoma cells. Oncogene 26, 5267-5279.
104. Junttila, M.R., Li, S.P., and Westermarck, J. (2008). Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J. 22, 954-965.
105. Kan, Z., Jaiswal, B.S., Stinson, J. et al. (2010). Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466, 869-873.
106. Kannaiyan, R., Manu, K.A., Chen, L., Li, F., Rajendran, P., Subramaniam, A., Lam, P., Kumar, A.P., and Sethi, G. (2011). Celastrol inhibits tumor cell proliferation and promotes apoptosis through the activation of c-Jun N-terminal kinase and suppression of PI3K/Akt signaling pathways. Apoptosis 16, 1028-1041.
107. Kannengiesser, C., Spatz, A., Michiels, S. et al. (2008). Gene expression signature associated with BRAF mutations in human primary cutaneous melanomas. Mol. Oncol. 1, 425-430.
108. Karasarides, M., Chiloeches, A., Hayward, R. et al. (2004). B-RAF is a therapeutic target in melanoma. Oncogene 23, 6292-6298.
109. Karin, M. (1995). The regulation of AP-1 activity by mitogen-activated protein kinases. J. Biol. Chem. 270, 16483-16486.
110. Ke, H., Harris, R., Coloff, J.L., Jin, J.Y., Leshin, B., Miliani De Marval, P., Tao, S., Rathmell, J.C., Hall, R.P., and Zhang, J.Y. (2010). The c-Jun NH2-terminal kinase 2 plays a dominant role in human epidermal neoplasia. Cancer Res. 70, 3080-3088.
111. Kennedy, N.J., and Davis, R.J. (2003). Role of JNK in tumor development. Cell Cycle 2, 199-201.
112. Keuling, A.M., Andrew, S.E., and Tron, V.A. (2010). Inhibition of p38 MAPK enhances ABT-737-induced cell death in melanoma cell lines: novel regulation of PUMA. Pigment Cell Melanoma Res. 23, 430-440.
113. Keyse, S.M. (2008). Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 27, 253-261.
114. Khanna, P., Yunkunis, T., Muddana, H.S., Peng, H.H., August, A., and Dong, C. (2010). p38 MAP kinase is necessary for melanoma-mediated regulation of VE-cadherin disassembly. Am. J. Physiol. Cell Physiol. 298, C1140-C1150.
115. Khatlani, T.S., Wislez, M., Sun, M. et al. (2007). c-Jun N-terminal kinase is activated in non-small-cell lung cancer and promotes neoplastic transformation in human bronchial epithelial cells. Oncogene 26, 2658-2666.
116. Kim, D.S., Hwang, E.S., Lee, J.E., Kim, S.Y., Kwon, S.B., and Park, K.C. (2003). Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. J. Cell Sci. 116, 1699-1706.
117. Kim, M.Y., Choi, T.Y., Kim, J.H., Lee, J.H., Kim, J.G., Sohn, K.C., Yoon, K.S., Kim, C.D., and Yoon, T.J. (2010). MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases. J. Dermatol. Sci. 60, 114-119.
118. Kingo, K., Aunin, E., Karelson, M., Ratsep, R., Silm, H., Vasar, E., and Koks, S. (2008). Expressional changes in the intracellular melanogenesis pathways and their possible role in the pathogenesis of vitiligo. J. Dermatol. Sci. 52, 39-46.
119. Kohno, M., and Pouyssegur, J. (2003). Pharmacological inhibitors of the ERK signaling pathway: application as anticancer drugs. Prog. Cell Cycle Res. 5, 219-224.
120. Kondoh, K., Sunadome, K., and Nishida, E. (2007). Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis. J. Biol. Chem. 282, 3058-3065.
121. Kortylewski, M., Heinrich, P.C., Kauffmann, M.E., Bohm, M., Mackiewicz, A., and Behrmann, I. (2001). Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells. Biochem. J. 357, 297-303.
122. Krasilnikov, M., Ivanov, V.N., Dong, J., and Ronai, Z. (2003). ERK and PI3K negatively regulate STAT-transcriptional activities in human melanoma cells: implications towards sensitization to apoptosis. Oncogene 22, 4092-4101.
123. Krishna, M., and Narang, H. (2008). The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell. Mol. Life Sci. 65, 3525-3544.
124. Kumar, R., Angelini, S., Czene, K., Sauroja, I., Hahka-Kemppinen, M., Pyrhonen, S., and Hemminki, K. (2003). BRAF mutations in metastatic melanoma: a possible association with clinical outcome. Clin. Cancer Res. 9, 3362-3368.
125. Kuphal, S., Poser, I., Jobin, C., Hellerbrand, C., and Bosserhoff, A.K. (2004). Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma. Oncogene 23, 8509-8519.
126. Lefevre, G., Calipel, A., Mouriaux, F., Hecquet, C., Malecaze, F., and Mascarelli, F. (2003). Opposite long-term regulation of c-Myc and p27Kip1 through overactivation of Raf-1 and the MEK/ERK module in proliferating human choroidal melanoma cells. Oncogene 22, 8813-8822.
127. Levy, C., Khaled, M., and Fisher, D.E. (2006). MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol. Med. 12, 406-414.
128. Liu, L., Cao, Y., Chen, C., Zhang, X., Mcnabola, A., Wilkie, D., Wilhelm, S., Lynch, M., and Carter, C. (2006). Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 66, 11851-11858.
129. Liu, J., Suresh Kumar, K.G., Yu, D., Molton, S.A., Mcmahon, M., Herlyn, M., Thomas-Tikhonenko, A., and Fuchs, S.Y. (2007). Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Oncogene 26, 1954-1958.
130. Longo, N., Yanez-Mo, M., Mittelbrunn, M., De La Rosa, G., Munoz, M.L., Sanchez-Madrid, F., and Sanchez-Mateos, P. (2001). Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells. Blood 98, 3717-3726.
131. Lopez-Bergami, P. (2009). The long arm of BRAF V600E gets to mTORC1. Pigment Cell Melanoma Res. 22, 244-245.
132. Lopez-Bergami, P., Habelhah, H., Bhoumik, A., Zhang, W., Wang, L.H., and Ronai, Z. (2005). RACK1 mediates activation of JNK by protein kinase C [corrected]. Mol. Cell 19, 309-320.
133. Lopez-Bergami, P., Huang, C., Goydos, J.S. et al. (2007). Rewired ERK-JNK signaling pathways in melanoma. Cancer Cell 11, 447-460.
134. Lopez-Bergami, P., Fitchman, B., and Ronai, Z. (2008). Understanding signaling cascades in melanoma. Photochem. Photobiol. 84, 289-306.
135. Lopez-Bergami, P., Kim, H., Dewing, A., Goydos, J., Aaronson, S., and Ronai, Z. (2010a). c-Jun regulates phosphoinositide-dependent kinase 1 transcription: implication for Akt and protein kinase C activities and melanoma tumorigenesis. J. Biol. Chem. 285, 903-913.
136. Lopez-Bergami, P., Lau, E., and Ronai, Z. (2010b). Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat. Rev. Cancer 10, 65-76.
137. MacCorkle, R.A., and Tan, T.H. (2004). Inhibition of JNK2 disrupts anaphase and produces aneuploidy in mammalian cells. J. Biol. Chem. 279, 40112-40121.
138. Mackeigan, J.P., Murphy, L.O., Dimitri, C.A., and Blenis, J. (2005). Graded mitogen-activated protein kinase activity precedes switch-like c-Fos induction in mammalian cells. Mol. Cell. Biol. 25, 4676-4682.
139. Malumbres, M., and Barbacid, M. (2003). RAS oncogenes: the first 30years. Nat. Rev. Cancer 3, 459-465.
140. Mansky, K.C., Sankar, U., Han, J., and Ostrowski, M.C. (2002). Microphthalmia transcription factor is a target of the p38 MAPK pathway in response to receptor activator of NF-kappa B ligand signaling. J. Biol. Chem. 277, 11077-11083.
141. Marquette, A., Andre, J., Bagot, M., Bensussan, A., and Dumaz, N. (2011). ERK and PDE4 cooperate to induce RAF isoform switching in melanoma. Nat. Struct. Mol. Biol. 18, 584-591.
142. Marshall, C.J. (1995). Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80, 179-185.
143. McCormick, F. (2010). How blocking Raf activates the MAPK pathway. Pigment Cell Melanoma Res. 23, 187-189.
144. McKay, M.M., and Morrison, D.K. (2007). Integrating signals from RTKs to ERK/MAPK. Oncogene 26, 3113-3121.
145. Meier, F., Schittek, B., Busch, S., Garbe, C., Smalley, K., Satyamoorthy, K., Li, G., and Herlyn, M. (2005). The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma. Front. Biosci. 10, 2986-3001.
146. Melnikova, V.O., Mourad-Zeidan, A.A., Lev, D.C., and Bar-Eli, M. (2006). Platelet-activating factor mediates MMP-2 expression and activation via phosphorylation of cAMP-response element-binding protein and contributes to melanoma metastasis. J. Biol. Chem. 281, 2911-2922.
147. Mhaidat, N.M., Zhang, X.D., Jiang, C.C., and Hersey, P. (2007). Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway. Clin. Cancer Res. 13, 1308-1314.
148. Michaloglou, C., Vredeveld, L.C., Soengas, M.S., Denoyelle, C., Kuilman, T., Van Der Horst, C.M., Majoor, D.M., Shay, J.W., Mooi, W.J., and Peeper, D.S. (2005). BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720-724.
149. Michaloglou, C., Vredeveld, L.C., Mooi, W.J., and Peeper, D.S. (2008). BRAF (E600) in benign and malignant human tumours. Oncogene 27, 877-895.
150. Mingo-Sion, A.M., Marietta, P.M., Koller, E., Wolf, D.M., and Van Den Berg, C.L. (2004). Inhibition of JNK reduces G2/M transit independent of p53, leading to endoreduplication, decreased proliferation, and apoptosis in breast cancer cells. Oncogene 23, 596-604.
151. Mooi, W.J., and Peeper, D.S. (2006). Oncogene-induced cell senescence - halting on the road to cancer. N. Engl. J. Med. 355, 1037-1046.
152. Morrison, D.K., and Davis, R.J. (2003). Regulation of MAP kinase signaling modules by scaffold proteins in mammals. Annu. Rev. Cell Dev. Biol. 19, 91-118.
153. Nazarian, R., Shi, H., Wang, Q. et al. (2010). Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973-977.
154. Newton, R.A., Cook, A.L., Roberts, D.W., Leonard, J.H., and Sturm, R.A. (2007). Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes. J. Invest. Dermatol. 127, 2216-2227.
155. Nitta, R.T., Del Vecchio, C.A., Chu, A.H., Mitra, S.S., Godwin, A.K., and Wong, A.J. (2011). The role of the c-Jun N-terminal kinase 2-alpha-isoform in non-small cell lung carcinoma tumorigenesis. Oncogene 30, 234-244.
156. Oba, J., Nakahara, T., Abe, T., Hagihara, A., Moroi, Y., and Furue, M. (2011). Expression of c-Kit, p-ERK and cyclin D1 in malignant melanoma: an immunohistochemical study and analysis of prognostic value. J. Dermatol. Sci. 62, 116-123.
157. Oka, M., and Kikkawa, U. (2005). Protein kinase C in melanoma. Cancer Metastasis Rev. 24, 287-300.
158. Omholt, K., Platz, A., Kanter, L., Ringborg, U., and Hansson, J. (2003). NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin. Cancer Res. 9, 6483-6488.
159. Ordan, O., Rotem, R., Jaspers, I., and Flescher, E. (2003). Stress-responsive JNK mitogen-activated protein kinase mediates aspirin-induced suppression of B16 melanoma cellular proliferation. Br. J. Pharmacol. 138, 1156-1162.
160. O'Shaughnessy, E.C., Palani, S., Collins, J.J., and Sarkar, C.A. (2011). Tunable signal processing in synthetic MAP kinase cascades. Cell 144, 119-131.
161. Owens, D.M., and Keyse, S.M. (2007). Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases. Oncogene 26, 3203-3213.
162. Packer, L.M., East, P., Reis-Filho, J.S., and Marais, R. (2009). Identification of direct transcriptional targets of (V600E) BRAF/MEK signalling in melanoma. Pigment Cell Melanoma Res. 22, 785-798.
163. Paraiso, K.H., Fedorenko, I.V., Cantini, L.P., Munko, A.C., Hall, M., Sondak, V.K., Messina, J.L., Flaherty, K.T., and Smalley, K.S. (2010). Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy. Br. J. Cancer 102, 1724-1730.
164. Pollock, P.M., Harper, U.L., Hansen, K.S. et al. (2003). High frequency of BRAF mutations in nevi. Nat. Genet. 33, 19-20.
165. Posen, Y., Kalchenko, V., Seger, R., Brandis, A., Scherz, A., and Salomon, Y. (2005). Manipulation of redox signaling in mammalian cells enabled by controlled photogeneration of reactive oxygen species. J. Cell Sci. 118, 1957-1969.
166. Prickett, T.D., Agrawal, N.S., Wei, X., Yates, K.E., Lin, J.C., Wunderlich, J.R., Cronin, J.C., Cruz, P., Rosenberg, S.A., and Samuels, Y. (2009). Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat. Genet. 41, 1127-1132.
167. Puri, P.L., Wu, Z., Zhang, P., Wood, L.D., Bhakta, K.S., Han, J., Feramisco, J.R., Karin, M., and Wang, J.Y. (2000). Induction of terminal differentiation by constitutive activation of p38 MAP kinase in human rhabdomyosarcoma cells. Genes Dev. 14, 574-584.
168. Rangaswami, H., and Kundu, G.C. (2007). Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol. Rep. 18, 909-915.
169. Recio, J.A., and Merlino, G. (2002). Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1. Oncogene 21, 1000-1008.
170. Rieber, M., and Rieber, M.S. (2008). Mcl-1 cleavage and sustained phosphorylation of c-Jun-N-terminal kinase mediate melanoma apoptosis induced by 2-acetyl furanonaphthoquinone: roles of Bcl-2 and p53. Cancer Biol. Ther. 7, 1206-1211.
171. Roberts, P.J., and Der, C.J. (2007). Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26, 3291-3310.
172. Rutberg, S.E., Goldstein, I.M., Yang, Y.M., Stackpole, C.W., and Ronai, Z. (1994). Expression and transcriptional activity of AP-1, CRE, and URE binding proteins in B16 mouse melanoma subclones. Mol. Carcinog. 10, 82-87.
173. Sabapathy, K., Hochedlinger, K., Nam, S.Y., Bauer, A., Karin, M., and Wagner, E.F. (2004). Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol. Cell 15, 713-725.
174. Saha, B., Singh, S.K., Sarkar, C., Bera, R., Ratha, J., Tobin, D.J., and Bhadra, R. (2006). Activation of the Mitf promoter by lipid-stimulated activation of p38-stress signalling to CREB. Pigment Cell Res. 19, 595-605.
175. Saldanha, G., Potter, L., Daforno, P., and Pringle, J.H. (2006). Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies. Clin. Cancer Res. 12, 4499-4505.
176. Santibanez, J.F., Iglesias, M., Frontelo, P., Martinez, J., and Quintanilla, M. (2000). Involvement of the Ras/MAPK signaling pathway in the modulation of urokinase production and cellular invasiveness by transforming growth factor-beta(1) in transformed keratinocytes. Biochem. Biophys. Res. Commun. 273, 521-527.
177. Sarkar, D., Su, Z.Z., Lebedeva, I.V., Sauane, M., Gopalkrishnan, R.V., Valerie, K., Dent, P., and Fisher, P.B. (2002). mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK. Proc. Natl. Acad. Sci. U S A 99, 10054-10059.
178. Satyamoorthy, K., Li, G., Gerrero, M.R., Brose, M.S., Volpe, P., Weber, B.L., Van Belle, P., Elder, D.E., and Herlyn, M. (2003). Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res. 63, 756-759.
179. Sauter, E.R., Yeo, U.C., Von Stemm, A. et al. (2002). Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res. 62, 3200-3206.
180. Schuierer, M.M., Bataille, F., Hagan, S., Kolch, W., and Bosserhoff, A.K. (2004). Reduction in Raf kinase inhibitor protein expression is associated with increased Ras-extracellular signal-regulated kinase signaling in melanoma cell lines. Cancer Res. 64, 5186-5192.
181. Selimovic, D., Hassan, M., Haikel, Y., and Hengge, U.R. (2008). Taxol-induced mitochondrial stress in melanoma cells is mediated by activation of c-Jun N-terminal kinase (JNK) and p38 pathways via uncoupling protein 2. Cell. Signal. 20, 311-322.
182. Shah, M., Stebbins, J.L., Dewing, A., Qi, J., Pellecchia, M., and Ronai, Z.A. (2009). Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis. Pigment Cell Melanoma Res. 22, 799-808.
183. Shah, M., Bhoumik, A., Goel, V. et al. (2010). A role for ATF2 in regulating MITF and melanoma development. PLoS Genet. 6, e1001258.
184. Sharma, A., Trivedi, N.R., Zimmerman, M.A., Tuveson, D.A., Smith, C.D., and Robertson, G.P. (2005). Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res. 65, 2412-2421.
185. Shemirani, B., and Crowe, D.L. (2002). Hypoxic induction of HIF-1alpha and VEGF expression in head and neck squamous cell carcinoma lines is mediated by stress activated protein kinases. Oral Oncol. 38, 251-257.
186. Sheridan, C., Brumatti, G., and Martin, S.J. (2008). Oncogenic B-RafV600E inhibits apoptosis and promotes ERK-dependent inactivation of Bad and Bim. J. Biol. Chem. 283, 22128-22135.
187. Shieh, J.M., Huang, T.F., Hung, C.F., Chou, K.H., Tsai, Y.J., and Wu, W.B. (2010). Activation of c-Jun N-terminal kinase is essential for mitochondrial membrane potential change and apoptosis induced by doxycycline in melanoma cells. Br. J. Pharmacol. 160, 1171-1184.
188. Shimo, T., Matsumura, S., Ibaragi, S., Isowa, S., Kishimoto, K., Mese, H., Nishiyama, A., and Sasaki, A. (2007). Specific inhibitor of MEK-mediated cross-talk between ERK and p38 MAPK during differentiation of human osteosarcoma cells. J. Cell Commun. Signal. 1, 103-111.
189. Shishodia, S., Sethi, G., Ahn, K.S., and Aggarwal, B.B. (2007). Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. Biochem. Pharmacol. 74, 118-130.
190. Smalley, K.S. (2003). A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int. J. Cancer 104, 527-532.
191. Smalley, K., and Eisen, T. (2000). The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative effects in B16 murine melanoma cells. FEBS Lett. 476, 198-202.
192. Smalley, K.S., Haass, N.K., Brafford, P.A., Lioni, M., Flaherty, K.T., and Herlyn, M. (2006). Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol. Cancer Ther. 5, 1136-1144.
193. Smalley, K.S., Contractor, R., Haass, N.K., Lee, J.T., Nathanson, K.L., Medina, C.A., Flaherty, K.T., and Herlyn, M. (2007). Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels. Br. J. Cancer 96, 445-449.
194. Smalley, K.S., Lioni, M., Dalla Palma, M. et al. (2008). Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol. Cancer Ther. 7, 2876-2883.
195. Sondak, V.K., and Flaherty, L.E. (2011). Targeted therapies: improved outcomes for patients with metastatic melanoma. Nat. Rev. Clin. Oncol. 8, 513-515.
196. Su, G.H., Hilgers, W., Shekher, M.C., Tang, D.J., Yeo, C.J., Hruban, R.H., and Kern, S.E. (1998). Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. Cancer Res. 58, 2339-2342.
197. Sumimoto, H., Miyagishi, M., Miyoshi, H., Yamagata, S., Shimizu, A., Taira, K., and Kawakami, Y. (2004). Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference. Oncogene 23, 6031-6039.
198. Timofeev, O., Lee, T.Y., and Bulavin, D.V. (2005). A subtle change in p38 MAPK activity is sufficient to suppress in vivo tumorigenesis. Cell Cycle 4, 118-120.
199. Tower, G.B., Coon, C.C., Benbow, U., Vincenti, M.P., and Brinckerhoff, C.E. (2002). Erk 1/2 differentially regulates the expression from the 1G/2G single nucleotide polymorphism in the MMP-1 promoter in melanoma cells. Biochim. Biophys. Acta 1586, 265-274.
200. Tsuiki, H., Tnani, M., Okamoto, I., Kenyon, L.C., Emlet, D.R., Holgado-Madruga, M., Lanham, I.S., Joynes, C.J., Vo, K.T., and Wong, A.J. (2003). Constitutively active forms of c-Jun NH2-terminal kinase are expressed in primary glial tumors. Cancer Res. 63, 250-255.
201. Ueda, Y., and Richmond, A. (2006). NF-kappaB activation in melanoma. Pigment Cell Res. 19, 112-124.
202. Uffort, D.G., Grimm, E.A., and Ellerhorst, J.A. (2009). NF-kappaB mediates mitogen-activated protein kinase pathway-dependent iNOS expression in human melanoma. J. Invest. Dermatol. 129, 148-154.
203. Uzgare, A.R., and Isaacs, J.T. (2004). Enhanced redundancy in Akt and mitogen-activated protein kinase-induced survival of malignant versus normal prostate epithelial cells. Cancer Res. 64, 6190-6199.
204. Van Raamsdonk, C.D., Bezrookove, V., Green, G., Bauer, J., Gaugler, L., O'brien, J.M., Simpson, E.M., Barsh, G.S., and Bastian, B.C. (2009). Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457, 599-602.
205. Van Raamsdonk, C.D., Griewank, K.G., Crosby, M.B. et al. (2010). Mutations in GNA11 in uveal melanoma. N. Engl. J. Med. 363, 2191-2199.
206. VanBrocklin, M.W., Verhaegen, M., Soengas, M.S., and Holmen, S.L. (2009). Mitogen-activated protein kinase inhibition induces translocation of Bmf to promote apoptosis in melanoma. Cancer Res. 69, 1985-1994.
207. Ventura, J.J., Tenbaum, S., Perdiguero, E., Huth, M., Guerra, C., Barbacid, M., Pasparakis, M., and Nebreda, A.R. (2007). p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat. Genet. 39, 750-758.
208. Villanueva, J., Vultur, A., Lee, J.T. et al. (2010). Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell 18, 683-695.
209. Vogt, P.K. (2001). Jun, the oncoprotein. Oncogene 20, 2365-2377.
210. Vojtek, A.B., and Der, C.J. (1998). Increasing complexity of the Ras signaling pathway. J. Biol. Chem. 273, 19925-19928.
211. Wagle, N., Emery, C., Berger, M.F. et al. (2011). Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J. Clin. Oncol. 29, 3085-3096.
212. Wagner, E.F., and Nebreda, A.R. (2009). Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer 9, 537-549.
213. Wang, C.C., Chiang, Y.M., Sung, S.C., Hsu, Y.L., Chang, J.K., and Kuo, P.L. (2008). Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells. Cancer Lett. 259, 82-98.
214. Weeraratna, A.T., Jiang, Y., Hostetter, G., Rosenblatt, K., Duray, P., Bittner, M., and Trent, J.M. (2002). Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1, 279-288.
215. Wellbrock, C., Rana, S., Paterson, H., Pickersgill, H., Brummelkamp, T., and Marais, R. (2008). Oncogenic BRAF regulates melanoma proliferation through the lineage specific factor MITF. PLoS ONE 3, e2734.
216. Weston, C.R., and Davis, R.J. (2007). The JNK signal transduction pathway. Curr. Opin. Cell Biol. 19, 142-149.
217. Whitmarsh, A.J., and Davis, R.J. (2007). Role of mitogen-activated protein kinase kinase 4 in cancer. Oncogene 26, 3172-3184.
218. Woods, D., Cherwinski, H., Venetsanakos, E., Bhat, A., Gysin, S., Humbert, M., Bray, P.F., Saylor, V.L., and Mcmahon, M. (2001). Induction of beta3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEK-extracellular signal-regulated kinase signaling pathway. Mol. Cell. Biol. 21, 3192-3205.
219. Wu, M., Hemesath, T.J., Takemoto, C.M., Horstmann, M.A., Wells, A.G., Price, E.R., Fisher, D.Z., and Fisher, D.E. (2000). c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev. 14, 301-312.
220. Yamada, S.D., Hickson, J.A., Hrobowski, Y. et al. (2002). Mitogen-activated protein kinase kinase 4 (MKK4) acts as a metastasis suppressor gene in human ovarian carcinoma. Cancer Res. 62, 6717-6723.
221. Yamanishi, D.T., Buckmeier, J.A., and Meyskens Jr, F.L. (1991). Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas. J. Invest. Dermatol. 97, 349-353.
222. Yazdi, A.S., Ghoreschi, K., Sander, C.A., and Rocken, M. (2010). Activation of the mitogen-activated protein kinase pathway in malignant melanoma can occur independently of the BRAF T1799A mutation. Eur. J. Dermatol. 20, 575-579.
223. Yi, M., Yang, J., Chen, X. et al. (2010). RASSF1A suppresses melanoma development by modulating apoptosis and cell-cycle progression. J. Cell. Physiol. 226, 2360-2369.
224. Yoon, S., and Seger, R. (2006). The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors 24, 21-44.
225. Young, P.R., Mclaughlin, M.M., Kumar, S. et al. (1997). Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase bind in the ATP site. J. Biol. Chem. 272, 12116-12121.
226. Yu, W., Imoto, I., Inoue, J., Onda, M., Emi, M., and Inazawa, J. (2007). A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity. Oncogene 26, 1178-1187.
227. Yu, H., Mcdaid, R., Lee, J. et al. (2009). The role of BRAF mutation and p53 inactivation during transformation of a subpopulation of primary human melanocytes. Am. J. Pathol. 174, 2367-2377.
228. Zehorai, E., Yao, Z., Plotnikov, A., and Seger, R. (2010). The subcellular localization of MEK and ERK - a novel nuclear translocation signal (NTS) paves a way to the nucleus. Mol. Cell. Endocrinol. 314, 213-220.
229. Zheng, B., Jeong, J.H., Asara, J.M., Yuan, Y.Y., Granter, S.R., Chin, L., and Cantley, L.C. (2009). Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol. Cell 33, 237-247.
230. Zhu, B.K., Wang, P., Zhang, X.D., Jiang, C.C., Chen, L.H., Avery-Kiejda, K.A., Watts, R., and Hersey, P. (2008). Activation of Jun N-terminal kinase is a mediator of vincristine-induced apoptosis of melanoma cells. Anticancer Drugs 19, 189-200.
231. Zhuang, L., Lee, C.S., Scolyer, R.A., Mccarthy, S.W., Palmer, A.A., Zhang, X.D., Thompson, J.F., Bron, L.P., and Hersey, P. (2005). Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma. J. Clin. Pathol. 58, 1163-1169.