Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Review

Main roads to melanoma

Authors: Giuseppe Palmieri, Mariaelena Capone, Maria Libera Ascierto, Giusy Gentilcore, David F Stroncek, Milena Casula, Maria Cristina Sini, Marco Palla, Nicola Mozzillo, Paolo A Ascierto

Published in: Journal of Translational Medicine | Issue 1/2009

Login to get access

Abstract

The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underlying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects regarding the main molecular changes responsible for the onset as well as the progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying the pathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of down- or up-regulation of various effectors acting on different molecular pathways.
Appendix
Available only for authorised users
Literature
1.
2.
Wolchok JD, Saenger YM: Current topics in melanoma. Curr Opin Oncol. 2007, 19: 116-20.PubMed
3.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho J, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA: Mutations of the BRAF gene in human cancer. Nature. 2002, 417: 949-54.PubMed
4.
5.
Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Brocker EB, LeBoit PE, Pinkel D, Bastian BC: Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005, 353: 2135-47.PubMed
6.
Mooi WJ, Peeper DS: Oncogene-induced cell senescence--halting on the road to cancer. New Engl J Med. 2006, 355: 1037-46.PubMed
7.
Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garre' M, Nuciforo PG, Bensimon A, Maestro R, Pelicci PG, d'Adda di Fagagna F: Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature. 2006, 444: 638-642.PubMed
8.
Hong SK, Pusapati RV, Powers JT, Johnson DG: Oncogenes and the DNA damage response - Myc and E2F1 engage the ATM signaling pathway to activate p53 and induce apoptosis. Cell Cycle. 2006, 5: 801-803.PubMed
9.
Di Micco R, Cicalese A, Fumagalli M, Dobreva M, Verrecchia A, Pelicci PG, di Fagagna F: DNA damage response activation in mouse embryonic fibroblasts undergoing replicative senescence and following spontaneous immortalization. Cell Cycle. 2008, 7: 3601-3606.PubMed
10.
Bennett DC: Familial melanoma genes, melanocyte immortalization and melanoma initiation. Melanocytes to Melanoma: The Progression to Malignancy. Edited by: Hearing VJ, Leong SPL. 2006, New Jersey: Humana Press, 183-96.
11.
Thompson JF, Scolyer RA, Kefford RF: Cutaneous melanoma. The Lancet. 2005, 365: 687-701.
12.
Haluska FG, Tsao H, Wu H, Haluska FS, Lazar A, Goel V: Genetic alterations in signaling pathways in melanoma. Clin Cancer Res. 2006, 12: 2301s-7s.PubMed
13.
Pomerantz J, Schreiber-Agus N, Liégeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, Cordon-Cardo C, DePinho RA: The Ink4a tumor suppressor gene product, 19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell. 1998, 92: 713-23.PubMed
14.
Soengas MS, Lowe SW: Apoptosis and melanoma chemoresistance. Oncogene. 2003, 22: 3138-51.PubMed
15.
Bowen AR, Hanks AN, Allen SM, Alexander A, Diedrich MJ, Grossman D: Apoptosis regulators and responses in human melanocytic and keratinocytic cells. J Invest Dermatol. 2003, 120: 48-55.PubMed
16.
Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, Melchi CF: Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer. 2005, 41: 45-60.PubMed
17.
Gilchrest BA, Eller MS, Geller AC, Yaar M: The pathogenesis of melanoma induced by ultraviolet radiation. New Engl J Med. 1999, 340: 1341-8.PubMed
18.
Jhappan C, Noonan FP, Merlino G: Ultraviolet radiation and cutaneous malignant melanoma. Oncogene. 2003, 22: 3099-112.PubMed
19.
Eide MJ, Weinstock MA: Association of UV index, latitude, and melanoma incidence in non-White populations--US surveillance, epidemiology, and end results (SEER) program, 1992 to 2001. Arch Dermatol. 2005, 141: 477-481.PubMed
20.
De Fabo EC, Noonan FP, Fears T, Merlino G: Ultraviolet B but not ultraviolet A radiation initiates melanoma. Cancer Res. 2004, 64: 6372-6.PubMed
21.
Wang SQ, Setlow R, Berwick M, Polsky D, Marghoob AA, Kopf AW, Bart RS: Ultraviolet A and melanoma: a review. J Am Acad Dermatol. 2001, 44: 837-46.PubMed
22.
Moan J, Dahlback A, Setlow RB: Epidemiological support for an hypothesis for melanoma induction indicating a role for UVA radiation. Photochem Photobiol. 1999, 70: 243-247.PubMed
23.
Oliveria S, Dusza S, Berwick M: Issues in the epidemiology of melanoma. Expert Rev Anticancer Ther. 2001, 1: 453-9.PubMed
24.
Garland C, Garland F, Gorham E: Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates. Ann Epidemiol. 2003, 13: 395-404.PubMed
25.
Takata M, Saida T: Genetic alteration in melanocytic tumors. J Dermat Science. 2006, 43: 1-10.
26.
Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W, Willemze R, Bavinck JN: Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol. 2001, 117: 294-300.PubMed
27.
Beaumont KA, Shekar SN, Newton RA, James MR, Stow JL, Duffy DL, Sturm RA: Receptor function, dominant negative activity and phenotype correlations for MC1R variant alleles. Hum Mol Genet. 2007, 16: 2249-2260.PubMed
28.
Kanetsky PA, Rebbeck TR, Hummer AJ, Panossian S, Armstrong BK, Kricker A, Marrett LD, Millikan RC, Gruber SB, Culver HA, Zanetti R, Gallagher RP, Dwyer T, Busam K, From L, Mujumdar U, Wilcox H, Begg CB, Berwick M: Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res. 2006, 66: 9330-9337.PubMed
29.
Raimondi S, Sera F, Gandini S, Iodice S, Caini S, Maisonneuve P, Fargnoli MC: MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer. 2008, 122: 2753-2760.PubMed
30.
Box NF, Duffy DL, Irving RE, Russell A, Chen W, Griffyths LR, Parsons PG, Green AC, Sturm RA: Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma. J Invest Dermatol. 2001, 116: 224-229.PubMed
31.
Giehl K: Oncogenic Ras in tumor progression and metastasis. Biol Chem. 2005, 386 (3): 193-205.PubMed
32.
Campbell PM, Der CJ: Oncogenic Ras and its role in tumor cell invasion and metastasis. Semin Cancer Biol. 2004, 14 (2): 105-14.PubMed
33.
Pritchard CA, Samuels ML, Bosch E, McMahon M: Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells. Mol Cell Biol. 1995, 15: 6430-42.PubMedCentralPubMed
34.
Beeram M, Patnaik A, Rowinsky EK: Raf: a strategic target for therapeutic development against cancer. J Clin Oncol. 2005, 23 (27): 6771-90.PubMed
35.
Emuss V, Garnett M, Mason C, Marais R: Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF. Cancer Res. 2005, 65: 9719-26.PubMed
36.
Zebisch A, Staber PB, Delavar A, Bodner C, Hiden K, Fischereder K, Janakiraman M, Linkesch W, Auner HW, Emberger W, Windpassinger C, Schimek MG, Hoefler G, Troppmair J, Sill H: Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Cancer Res. 2006, 66: 3401-8.PubMed
37.
Lee JW, Soung YH, Kim SY, Park WS, Nam SW, Min WS, Kim SH, Lee JY, Yoo NJ, Lee SH: Mutational analysis of the ARAF gene in human cancers. APMIS. 2005, 113: 54-7.PubMed
38.
Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA: High prevalence of BRAF mutations in papillary thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signalling pathway in papillary carcinoma. Cancer Res. 2003, 63 (7): 1454-7.PubMed
39.
Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR, Weber BL: BRAF and Ras mutations in human lung cancer and melanoma. Cancer Res. 2002, 62 (23): 6997-7000.PubMed
40.
Tannapfel A, Sommerer F, Benicke M, Katalinic A, Uhlmann D, Witzigmann H, Hauss J, Wittekind C: Mutation of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma. Gut. 2003, 52 (5): 706-12.PubMedCentralPubMed
41.
Palmieri G, Casula M, Sini MC, Ascierto PA, Cossu A: Issues affecting molecular staging in the management of patients with melanoma. J Cell Mol Med. 2007, 11: 1052-1068.PubMedCentralPubMed
42.
Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R: Cancer Genome Project. Mechanism of activation of tha Ras-Erk signaling pathaway by oncogenic mutation on BRAF. Cell. 2004, 116: 855-867.PubMed
43.
Carreira S, Goodall J, Aksan I, La Rocca SA, Galibert MD, Denat L, Larue L, Goding CR: Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression. Nature. 2005, 433: 764-9.PubMed
44.
Casula M, Colombino M, Satta MP, Cossu A, Ascierto PA, Bianchi-Scarrà G, Castiglia D, Budroni M, Rozzo C, Manca A, Lissia A, Carboni A, Petretto E, Satriano SM, Botti G, Mantelli M, Ghiorzo P, Stratton MR, Tanda F, Palmieri G, Italian Melanoma Intergroup Study: Braf gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup study. J Clin Oncol. 2004, 22: 286-92.PubMed
45.
Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM, Meltzer PS: High frequency of BRAF mutations in nevi. Nat Genet. 2003, 33 (1): 19-20.PubMed
46.
Dong J, Phelps RG, Qiao R, Yao S, Benard O, Ronai Z, Aaronson SA: BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res. 2003, 63 (14): 3883-5.PubMed
47.
Greene VR, Johnson MM, Grimm EA, Ellerhorst JA: Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma. J Invest Dermatol. 2009, 129: 1483-1488.PubMedCentralPubMed
48.
Patton EE, Widlund HR, Kutok JL, Kopani KR, Amatruda JF, Murphey RD, Berghmans S, Mayhall EA, Traver D, Fletcher CD, Aster JC, Granter SR, Look AT, Lee C, Fisher DE, Zon LI: BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol. 2005, 15: 249-54.PubMed
49.
Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, Horst van der CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS: BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005, 436: 720-724.PubMed
50.
Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR: Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 2008, 132: 363-374.PubMedCentralPubMed
51.
Michaloglou C, Vredeveld LC, Mooi WJ, Peeper DS: BRAF(E600) in benign and malignant human tumours. Oncogene. 2008, 27: 877-895.PubMed
52.
Dhomen N, Reis-Filho JS, da Rocha Dias S, Hayward R, Savage K, Delmas V, Larue L, Pritchard C, Marais R: Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009, 15: 294-303.PubMed
53.
Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, Calista D, Kanetsky PA, Pinkel D, Bastian BC: MC1R germline variants confer risk for BRAF-mutant melanoma. Science. 2006, 313: 521-2.PubMed
54.
Sensi M, Nicolini G, Petti C, Bersani I, Lozupone F, Molla A, Vegetti C, Nonaka D, Mortarini R, Parmiani G, Fais S, Anichini A: Mutually exclusive N-RasQ61R and BRAF V600E mutations at the single-cell level in the same human melanoma. Oncogene. 2006, 25: 3357-64.PubMed
55.
Jiveskog S, Ragnarsson-Olding B, Platz A, Ringborg U: N-RAS mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin. J Invest Dermatol. 1998, 111: 757-761.PubMed
56.
El Shabrawi Y, Radner H, Muellner K, Langmann G, Hoefler G: The role of UV-radiation in the development of conjunctival malignant melanoma. Acta Ophthalmol Scand. 1999, 77: 31-32.PubMed
57.
Ashida A, Takata M, Murata H, Kido K, Saida T: Pathological activation of KIT in metastatic tumors of acral and mucosal melanomas. Int J Cancer. 2009, 124: 862-868.PubMed
58.
Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J, Town A, Harlow A, Cruz F, Azar S, Rubin BP, Muller S, West R, Heinrich MC, Corless CL: KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008, 14: 6821-6828.PubMed
59.
Stone S, Ping J, Dayananth P, Tavtigian SV, Katcher H, Parry D, Gordon P, Kamb A: Complex Structure and Regulation of the P16 (MTS1) Locus. Cancer Research. 1995, 55: 2988-2994.PubMed
60.
Pho L, Grossman D, Laechman SA: Melanoma genetics: a review of genetic factors and clinical phenotypes in familial melanoma. Current Opinion in Oncology. 2006, 18: 173-9.PubMed
61.
Quelle DE, Zindy F, Ashmun RA, Sherr CJ: Alternative reading frames of INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell. 1995, 83: 993-1000.PubMed
62.
Pacifico A, Leone G: Role of p53 and CKN2A inactivation in human squamous cell carcinomas. J Biomed Biotechnol. 2007, 2007 (3): 43418-PubMedCentralPubMed
63.
Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM: MDM2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 2000, 275 (12): 8945-51.PubMed
64.
Stott FJ, Bates S, James MC, McConnell BB, Starborg M, Brookes S, Palmero I, Ryan K, Hara E, Vousden KH, Peters G: The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2. Embo J. 1998, 17: 5001-5014.PubMedCentralPubMed
65.
Tsao H, Zhang X, Kwitkiwski K, Finkelstein DM, Sober AJ, Haluska FG: Low Prevalence of Germline CDKN2A and CDK4 Mutations in Patients With Early-Onset Melanoma. Arch Dermatol. 2000, 136: 1118-1122.PubMed
66.
Piepkorn M: Melanoma genetics: An update with focus on the CDKN2A(p16)/ARF tumor suppressors. J Am Acad Dermatol. 2000, 42: 705-722.PubMed
67.
Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 1997, 88: 323-331.PubMed
68.
Box NF, Terzian T: The role of p53 in pigmentation, tanning and melanoma. Pigment Cell Melanoma Res. 2008, 21: 525-533.PubMed
69.
Goldstein AM, Landi MT, Tsang S, Fraser MC, Munroe DJ, Tucker MA: Association of MC1R Variants and Risk of Melanoma in Melanoma-Prone Families with CDKN2A Mutations. Cancer Epidemiol Biomarkers Prev. 2005, 14 (9):
70.
Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N, Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA, Melanoma Genetics Consortium: Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002, 94 (12): 894-903.PubMed
71.
Chaudru V, Chompret A, Bressac-de Paillerets B, Spatz A, Avri MF, Demenais F: Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. Journal of the National Cancer Institute. 2004, 96: 785-95.PubMed
72.
Puig S, Malvehy J, Badenas C, Ruiz A, Jimenez D, Cuellar F, Azon A, Gonzàlez U, Castel T, Campoy A, Herrero J, Martí R, Brunet-Vidal J, Milà M: Role of the CDKN2A Locus in patients with multiple primary melanomas. J Clin Oncol. 2005, 23: 3043-3051.PubMed
73.
Eliason MJ, Hansen CB, Hart M, Porter-Gill P, Chen W, Sturm RA, Bowen G, Florell SR, Harris RM, Cannon-Albright LA, Swinyer L, Leachman SA: Multiple primary melanomas in a CDKN2A mutation carrier exposed to ionizing radiation. Arch Dermatol. 2007, 143 (11): 1409-12.PubMed
74.
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997, 275: 1943-1947.PubMed
75.
Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumour suppressor PTEN. Science. 1998, 280: 1614-1617.PubMed
76.
Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB, Pandolfi PP: Impaired Fas response and autoimmunity in PTEN +/- mice. Science. 1999, 285: 2122-2125.PubMed
77.
Li J, Simpson L, Takahashi M, Miliaresis C, Myers MP, Tonks N, Parsons R: The PTEN/MMAC1 tumour suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene. Cancer Res. 1998, 58: 5667-5672.PubMed
78.
Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Rulnd J, Penninger JM, Siderovski DP, Mak TW: Negative regulation of PKB/Akt-dependent cell survival by the tumour suppressor PTEN. Cell. 1998, 95: 29-39.PubMed
79.
Datta SR, Brunet A, Greenberg ME: Cellular survival: A play in three Akts. Genes Dev. 1999, 13: 2905-2927.PubMed
80.
Brazil DP, Park J, Hemmings BA: PKB binding proteins: getting in on the Akt. Cell. 2002, 111: 293-303.PubMed
81.
Nicholson KM, Anderson NG: The protein kinase B/Akt signalling pathway in human malignancy. Cell Signalling. 2002, 14: 381-95.PubMed
82.
Chen WS, Xu PZ, Gottlob K, Chen ML, Sokol K, Shiyanova T, Roninson I, Weng W, Suzuki R, Tobe K, Kadowaki T, Hay N: Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. 2001, 15: 2203-8.PubMedCentralPubMed
83.
Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, Kaestner KH, Bartolomei MS, Shulman GI, Birnbaum MJ: Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB). Science. 2001, 292: 1728-31.PubMed
84.
Satyamoorthy K, Li G, Vaidya B, Patel D, Herlyn M: Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogen-activated protein kinase and beta-catenin pathways. Cancer Res. 2001, 61: 7318-24.PubMed
85.
Dhawan P, Singh AB, Ellis DL, Richmond A: Constitutive Activation Akt/Protein kinase B in Melanoma Leads to Up-Regulation of Nuclear factor-kB and Tumor Progression. Cancer Res. 2002, 62: 7335-7342.PubMed
86.
87.
Dahia PL: PTEN, a unique tumor suppressor gene. Endocr Relat Cancer. 2000, 7: 115-129.PubMed
88.
Kandel ES, Hay N: The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Exp Cell Res. 1999, 253: 210-229.PubMed
89.
Downward J: PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol. 2004, 15: 177-182.PubMed
90.
Vivanco I, Sawyers CL: The phosphatidylinositol 3-kinase AKT pathwayin human cancer. Nat Rev Cancer. 2002, 2: 489-501.PubMed
91.
Staal SP: Molecular cloning of the Akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natal Acad Sci. 1987, 84: 5034-7.
92.
Bellacosa A, de Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, Wan M, Dubeau L, Scambia G, Masciullo V, Ferrandina G, Benedetti Panici P, Mancuso S, Neri G, Testa JR: Molecular alterations of the Akt2 oncogene in ovarian and breast carcinomas. Int J Cancer. 1995, 64: 280-5.PubMed
93.
Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, Kester M, Sandirasegarane L, Robertson GP: Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 2004, 64: 7002-10.PubMed
94.
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE: High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004, 304 (5670): 554-PubMed
95.
Samuels Y, Diaz LA, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE: Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell. 2005, 7: 561-73.PubMed
96.
Omholt K, Krockel D, Ringborg U, Hansson J: Mutations of PIK3CA are rare in cutaneous melanoma. Melanoma Res. 2006, 16: 197-200.PubMed
97.
Curtin JA, Stark MS, Pinkel D, Hayward NK, Bastian BC: PI3-kinase subunits are infrequent somatic targets in melanoma. J Invest Dermatol. 2006, 126: 1660-3.PubMed
98.
Blume-Jensen P, Hunter T: Oncogenic kinase signalling. Nature. 2001, 411: 355-365.PubMed
99.
Plas DR, Thompson CB: Akt-dependent transformation: there is more to growth than just surviving. Oncogene. 2005, 24: 7435-7442.PubMed
100.
Stiles B, Groszer M, Wang S, Jiao J, Wu H: PTENless means more. Dev Biol. 2004, 273: 175-184.PubMed
101.
Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997, 91: 231-241.PubMed
102.
Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, Frisch S, Reed JC: Regulation of cell death protease caspase-9 by phosphorylation. Science. 1998, 282: 1318-1321.PubMed
103.
Mayo LD, Donner DB: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci. 2001, 98: 11598-11603.PubMedCentralPubMed
104.
Gottlieb TM, Leal JF, Seger R, Taya Y, Oren M: Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of apoptosis. Oncogene. 2002, 21: 1299-1303.PubMed
105.
Oren M, Damalas A, Gottlieb T, Michael D, Taplick J, Leal JF, Maya R, Moas M, Seger R, Taya Y, Ben-Ze'ev A: Regulation of p53: intricate loops and delicate balances. Biochem Pharmacol. 2002, 64: 865-871.PubMed
106.
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999, 96: 857-868.PubMed
107.
Romashkova JA, Makarov SS: NF-κB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 1999, 401: 86-90.PubMed
108.
Wan YS, Wang ZQ, Shao Y, Voorhees JJ, Fisher GJ: Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. Int J Oncol. 2001, 18: 461-6.PubMed
109.
Waldmann V, Wacker J, Deichmann M: Mutations of the activation-associated phosphorylation sites at codons 308 and 473 of protein kinase B are absent in human melanoma. Arch Dermatol Res. 2001, 293: 368-72.PubMed
110.
Waldmann V, Wacker J, Deichmann M: Absence of mutations in the pleckstrin homology (PH) domain of protein kinase B (PKB/Akt) in malignant melanoma. Melanoma Res. 2002, 12: 45-50.PubMed
111.
Davies MA, Stemke-Hale K, Tellez C, Calderone TL, Deng W, Prieto VG, Lazar AJ, Gershenwald JE, Mills GB: A novel AKT3 mutation in melanoma tumours and cell lines. Br J Cancer. 2008, 99: 1265-1268.PubMedCentralPubMed
112.
Krasilnikov M, Adler V, Fuchs SY, Dong Z, Haimovitz-Friedman A, Herlyn M, Ronai Z: Contribution of phosphatidylinositol 3-kinase to radiation resistance in human melanoma cells. Mol Carcinog. 1999, 24: 64-9.PubMed
113.
Simpson L, Parsons R: PTEN: life as a tumor suppressor. Exp Cell Res. 2001, 264: 29-41.PubMed
114.
Maehama T, Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998, 273: 13375-13378.PubMed
115.
Vazquez F, Sellers WR: The PTEN tumor suppressor protein: an antagonist of phosphoinositide 3-kinase signaling. Biochim Biophys Acta. 2000, 1470 (1): M21-35.PubMed
116.
Bonneau D, Longy M: Mutations of the human PTEN gene. Hum Mutat. 2000, 16 (2): 109-22.PubMed
117.
Maehama T, Taylor GS, Dixon JE: PTEN and myotubularin: novel phosphoinositide phosphatases. Annu Rev Biochem. 2001, 70: 247-279.PubMed
118.
Ali IU, Schriml LM, Dean M: Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. J Nat Cancer Inst. 1999, 91: 1922-1932.PubMed
119.
Tsao H, Zhang X, Benoit E, Haluska FG: Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines. Oncogene. 1998, 16 (26): 3397-402.PubMed
120.
Egger G, Liang G, Aparicio A, Jones PA: Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004, 429: 457-63.PubMed
121.
Dahia PL, Aguiar RC, Alberta J, Kum JB, Caron S, Sill H, Marsh DJ, Ritz J, Freedman A, Stiles C, Eng C: 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: 185-93.PubMed
122.
Salvesen HB, MacDonald N, Ryan A, Jacobs IJ, Lynch ED, Akslen LA, Das S: PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int J Cancer. 2001, 91 (1): 22-6.PubMed
123.
Fuse N, Yasumoto K, Takeda K, Amae S, Yoshizawa M, Udono T, Takahashi K, Tamai M, Tomita Y, Tachibana M, Shibahara S: Molecular cloning of cDNA encoding a novel microphthalmia-associated transcription factor isoform with a distinct amino-terminus. J Biochem. 1999, 126: 1043-1051.PubMed
124.
Hodgkinson CA, Moore KJ, Nakayama A, Steingrímsson E, Copeland NG, Jenkins NA, Arnheiter H: Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell. 1993, 74: 395-404.PubMed
125.
Hughes AE, Newton VE, Liu XZ, Read AP: A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1. Nat Genet. 1994, 7: 509-512.PubMed
126.
Bentley NJ, Eisen T, Goding CR: Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator. Mol Cell Biol. 1994, 14: 7996-8006.PubMedCentralPubMed
127.
Hemesath TJ, Steingrímsson E, McGill G, Hansen MJ, Vaught J, Hodgkinson CA, Arnheiter H, Copeland NG, Jenkins NA, Fisher DE: Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. 1994, 8: 2770-2780.PubMed
128.
Yasumoto K, Yokoyama K, Shibata K, Tomita Y, Shibahara S: Micropthalmia-associated transcription factor as a regulator for melanocytespecific transcription of the human tyrosinase gene. Mol Cell Biol. 1994, 14: 8058-8070.PubMedCentralPubMed
129.
Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S: Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J Biol Chem. 1997, 272: 503-509.PubMed
130.
Steingrímsson E, Copeland NG, Jenkins NA: Melanocytes and the microphthalmia transcription factor network. Annu Rev Genet. 2004, 38: 365-411.PubMed
131.
Selzer E, Wacheck V, Lucas T, Heere-Ress E, Wu M, Weilbaecher KN, Schlegel W, Valent P, Wrba F, Pehamberger H, Fisher D, Jansen B: The melanocyte-specific isoform of the microphthalmia transcription factor affects the phenotype of human melanoma. Cancer Res. 2002, 62: 2098-2103.PubMed
132.
Opdecamp K, Nakayama A, Nguyen MT, Hodgkinson CA, Pavan WJ, Arnheiter H: Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the MITF basic-helix-loop-helix-zipper transcription factor. Development. 1997, 124: 2377-2386.PubMed
133.
Wellbrock C, Marais R: Elevated expression of MITF counteracts B-RAF stimulated melanocyte and melanoma cell proliferation. J Cell Biol. 2005, 170: 703-708.PubMedCentralPubMed
134.
Hoek KS, Eichhoff OM, Schlegel NC, Döbbeling U, Kobert N, Schaerer L, Hemmi S, Dummer R: In vivo switching of human melanoma cells between proliferative and invasive states. Cancer Res. 2008, 68: 650-656.PubMed
135.
Salti GI, Manougian T, Farolan M, Shilkaitis A, Majumdar D, Das Gupta TK: Microphthalmia transcription factor: a new prognostic marker in intermediate-thickness cutaneous malignant melanoma. Cancer Res. 2000, 60: 5012-5016.PubMed
136.
Zhuang L, Lee CS, Scolyer RA, McCarthy SW, Zhang XD, Thompson JF, Hersey P: Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma. Mod Pathol. 2007, 20: 416-426.PubMed
137.
King R, Googe PB, Weilbaecher KN, Mihm MC, Fisher DE: Microphthalmia transcription factor. A sensitive and specific melanocyte marker for melanoma diagnosis. Am J Path. 1999, 155: 731-738.PubMedCentralPubMed
138.
Miettinen M, Fernandez M, Franssila K, Gatalica Z, Lasota J, Sarlomo-Rikala M: Micropthamia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Am J Surg Pathol. 2001, 25: 205-211.PubMed
139.
Chang KL, Folpe AL: Diagnostic utility of microphthalmia transcription factor in malignant melanoma and other tumors. Adv Anat Pathol. 2001, 8: 273-275.PubMed
140.
Levy C, Khaled M, Fisher DE: MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med. 2006, 12: 406-14.PubMed
141.
Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR: Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 2005, 436: 117-22.PubMed
142.
Garraway LA, Sellers WR: Lineage dependency and lineage-survival oncogenes in human cancer. Nat Rev Cancer. 2006, 6: 593-602.PubMed
143.
Loercher AE, Tank EM, Delston RB, Harbour JW: MITF links differentiation with cell cycle arrest in melanocytes by transcriptional activation of INK4A. J Cell Biol. 2005, 168: 35-40.PubMedCentralPubMed
144.
Du J, Widlund HR, Horstmann MA, Ramaswamy S, Ross K, Huber WE, Nishimura EK, Golub TR, Fisher DE: Critical role of CDK2 for melanoma growth linked to its melanocytespecific transcriptional regulation by MITF. Cancer Cell. 2004, 6: 565-76.PubMed
145.
McGill GG, Horstmann M, Widlund HR, Du J, Motyckova G, Nishimura EK, Lin YL, Ramaswamy S, Avery W, Ding HF, Jordan SA, Jackson IJ, Korsmeyer SJ, Golub TR, Fisher DE: Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell. 2002, 109: 707-18.PubMed
146.
Goding CR: Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev. 2000, 14: 1712-1728.PubMed
147.
Thomson JA, Murphy K, Baker E, Sutherland GR, Parsons PG, Sturm RA, Thomson F: The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells. Oncogene. 1995, 11: 691-700.PubMed
148.
Hemesath TJ, Price ER, Takemoto C, Badalian T, Fisher DE: MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. Nature. 1998, 391: 298-301.PubMed
149.
Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R: Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol. 1998, 142: 827-835.PubMedCentralPubMed
150.
Bertolotto C, Bille K, Ortonne JP, Ballotti R: Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmiagene product. Cell Sci. 1996, 134: 747-755.
151.
Polakis P: Wnt signaling and cancer. Genes Dev. 2000, 14: 1837-1851.PubMed
152.
Dorsky RI, Moon RT, Raible DW: Control of neural crest cell fate by the Wnt signalling pathway. Nature. 1998, 396: 370-373.PubMed
153.
Dorsky RI, Moon RT, Raible DW: Environmental signals and cell fate specification in premigratory neural crest. Bioessays. 2000, 22: 708-716.PubMed
154.
Peifer M, Polakis P: Wnt signaling in oncogenesis and embryogenesisa look outside the nucleus. Science. 2000, 287: 1606-1609.PubMed
155.
You L, He B, Xu Z, Uematsu K, Mazieres J, Fujii N, Mikami I, Reguart N, McIntosh JK, Kashani-Sabet M, McCormick F, Jablons DM: An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth. Cancer Res. 2004, 64: 5385-5389.PubMed
156.
Kashani-Sabet M, Range J, Torabian S, Nosrati M, Simko J, Jablons DM, Moore DH, Haqq C, Miller III, Sagebiel RW: A multi-marker assay to distinguish malignant melanomas from benign nevi. Proc Natl Acad Sci USA. 2009, 106: 6268-6272.PubMedCentralPubMed
157.
Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P: Stabilization of β-catenin by genetic defects in melanoma cell lines. Science. 1997, 275: 1790-1792.PubMed
158.
Rimm DL, Caca K, Hu G, Harrison FB, Fearon ER: Frequent nuclear/cytoplasmic localization of β-catenin without exon 3 mutations in malignant melanoma. Am J Path. 1999, 154: 325-329.PubMedCentralPubMed
159.
Morgan T: The theory of the gene. Am Nat. 1917, 51: 513-544.
160.
Robbins J, Blondel BJ, Gallahan D, Callahan R: Mouse mammary tumor gene int-3: a member of the Notch gene family transforms mammary epithelial cells. J Virol. 1992, 66: 2594-2599.PubMedCentralPubMed
161.
Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G, Callahan R: Expression of an activated Notch-related int-3 trangene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev. 1992, 6: 345-355.PubMed
162.
Lardelli M, Williams R, Lendahl U: Notch-related genes in animal development. Int J Dev Biol. 1995, 39: 769-780.PubMed
163.
Mumm JS, Schroeter EH, Saxena MT, Griesemer A, Tian X, Pan DJ, Ray WJ, Kopan R: A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol Cell. 2000, 5: 197-206.PubMed
164.
Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, Cumano A, Roux P, Black RA, Israël A: A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell. 2000, 5: 207-216.PubMed
165.
Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R, Israel A: Signalling downstream of activated mammalian Notch. Nature. 1995, 377: 355-358.PubMed
166.
Lai EC: Protein degradation: four E3s for the notch pathway. Curr Biol. 2002, 12: R74-R78.PubMed
167.
Lai EC: Notch signaling: control of cell communication and cell fate. Development. 2004, 131: 965-973.PubMed
168.
Artavanis-Tsakonas S, Rand MD, Lake RJ: Notch signaling: cell fate control and signal integration in development. Science. 1999, 284: 770-776.PubMed
169.
Jeffries S, Capobianco AJ: Neoplastic transformation by Notch requires nuclear localization. Mol Cell Biol. 2000, 20: 3928-3941.PubMedCentralPubMed
170.
Allman D, Punt JA, Izon DJ, Aster JC, Pear WS: An invitation to T and more: notch signaling in lymphopoiesis. Cell. 2002, 109: S1-S11.PubMed
171.
Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, Sklar J: TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991, 66: 649-61.PubMed
172.
Sriuranpong V, Borges MW, Ravi RK, Arnold DR, Nelkin BD, Baylin SB, Ball DW: Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res. 2001, 61: 3200-5.PubMed
173.
Gestblom C, Grynfeld A, Ora I, Ortoft E, Larsson C, Axelson H, Sandstedt B, Cserjesi P, Olson EN, Påhlman S: The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas. Lab Invest. 1999, 79: 67-79.PubMed
174.
Grynfeld A, Påhlman S, Axelson H: Induced neuroblastoma cell differentiation, associated with transient HES-1 activity and reduced HASH-1 expression, is inhibited by Notch1. Int J Cancer. 2000, 88: 401-10.PubMed
175.
Zagouras P, Stifani S, Blaumueller CM, Carcangiu ML, Artavanis-Tsakonas S: Alterations in Notch signaling in neoplastic lesions of the human cervix. Proc Natl Acad Sci USA. 1995, 92: 6414-8.PubMedCentralPubMed
176.
Talora C, Sgroi DC, Crum CP, Dotto GP: Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation. Genes Dev. 2002, 16: 2252-63.PubMedCentralPubMed
177.
Shou J, Ross S, Koeppen H, de Sauvage FJ, Gao WQ: Dynamics of notch expression during murine prostate development and tumorigenesis. Cancer Res. 2001, 61: 7291-7.PubMed
178.
Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, Hui CC, Clevers H, Dotto GP, Radtke F: Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003, 33: 416-21.PubMed
179.
Rangarajan A, Talora C, Okuyama R, Nicolas M, Mammucari C, Oh H, Aster JC, Krishna S, Metzger D, Chambon P, Miele L, Aguet M, Radtke F, Dotto GP: Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J. 2001, 20: 3427-36.PubMedCentralPubMed
180.
Lowell S, Jones P, Le Roux I, Dunne J, Watt FM: Stimulation of human epidermal differentiation by δ-notch signalling at the boundaries of stem-cell clusters. Curr Biol. 2000, 10: 491-500.PubMed
181.
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R: Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res. 2004, 64: 5270-82.PubMed
182.
Massi D, Tarantini F, Franchi A, Paglierani M, Di Serio C, Pellerito S, Leoncini G, Cirino G, Geppetti P, Santucci M: Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma. Modern Pathology. 2006, 19: 246-259.PubMed
183.
Pinnix CC, Lee JT, Liu ZJ, McDaid R, Balint K, Beverly LJ, Brafford PA, Xiao M, Himes B, Zabierowski SE, Yashiro-Ohtani Y, Nathanson KL, Bengston A, Pollock PM, Weeraratna AT, Nickoloff BJ, Pear WS, Capobianco AJ, Herlyn M: Active Notch1 confers a transformed phenotype to primary human melanocytes. Cancer Res. 2009, 69: 5312-5320.PubMedCentralPubMed
184.
Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH: Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell. 2002, 110: 751-762.PubMed
185.
Li G, Satyamoorthy K, Herlyn M: N-cadherin-mediated intercellular interactions promote survival and migration f melanoma cells. Cancer Res. 2001, 61: 3819-3825.PubMed
186.
Cheng P, Zlobin A, Volgina V, Gottipati S, Osborne B, Simel EJ, Miele L, Gabrilovich DI: Notch-1 regulates NF-kB activity in hemopoietic progenitor cells. J Immunol. 2001, 167: 4458-4467.PubMed
187.
Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA: Notch1 augments Nf-kB activity by facilitating its nuclear retention. EMBO J. 2006, 25: 129-138.PubMedCentralPubMed
188.
Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, Rudolf M, Siziopikou K, Kast WM, Miele L: Activation of Notch1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Na Med. 2002, 8: 979-986.
189.
Kiaris H, Politi K, Grimm LM, Szabolcs M, Fisher P, Efstratiadis A, Artavanis-Tsakonas S: Modulation of Notch signaling elicits signature tumors and inhibits hras1-induced oncogenesis in the mouse mammary epithelium. Am J Pathol. 2004, 165: 695-705.PubMedCentralPubMed
190.
Grimm EA, Ellerhorst J, Tang CH, Ekmekcioglu S: Constitutive intracellular production of iNOS and NO in human melanoma: possible role in regulation of growth and resistance to apoptosis. Nitric Oxide. 2008, 19: 133-137.PubMedCentralPubMed
191.
Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, Le J, Koh SI, Kimura T, Green SJ, Mak TW, Taniguchi T, Vilcek J: Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science. 1994, 263: 1612-1615.PubMed
192.
Martin E, Nathan C, Xie QW: Role of interferon regulatory factor 1 in induction of nitric oxide synthase. J Exp Med. 1994, 180: 977-984.PubMed
193.
Xie QW, Kashiwabara Y, Nathan C: Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem. 1994, 269: 4705-4708.PubMed
194.
Adcock IM, Brown CR, Kwon O, Barnes PJ: Oxidative stress induces NF kappa B DNA binding and inducible NOS mRNA in human epithelial cells. Biochem Biophys Res Commun. 1994, 199: 1518-1524.PubMed
195.
Meyskens FL, McNulty SE, Buckmeier JA, Tohidian NB, Spillane TJ, Kahlon RS, Gonzalez RI: Aberrant redox regulation in human metastatic melanoma cells compared to normal melanocytes. Free Radic Biol Med. 2001, 31: 799-808.PubMed
196.
Zhang J, Peng B, Chen X: Expression of nuclear factor kappaB, inducible nitric oxide syntheses, and vascular endothelial growth tactor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome. Clin Cancer Res. 2005, 11: 7334-7343.PubMed
197.
MacMicking J, Xie QW, Nathan C: Nitric oxide and macrophage function. Rev Immunol. 1997, 15: 323-350.
198.
Bredt DS: Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic Res. 1999, 31: 577-596.PubMed
199.
Geller DA, Billiar TR: Molecular biology of nitric oxide synthases. Cancer Metastasis Rev. 1998, 17: 7-23.PubMed
200.
Massi D, Franchi A, Sardi I, Magnelli L, Paglierani M, Borgognoni L, Maria Reali U, Santucci M: Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions. J Pathol. 2001, 194: 194-200.PubMed
201.
Xie K, Huang S, Dong Z, Juang SH, Gutman M, Xie QW, Nathan C, Fidler IJ: Transfection with the inducible nitric oxide syntheses gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J Exp Med. 1995, 181: 1333-1343.PubMed
202.
Xie K, Wang Y, Huang S, Xu L, Bielenberg D, Salas T, McConkey DJ, Jiang W, Fidler IJ: Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with downregulation of Bcl-2. Oncogene. 1997, 15 (7): 771-9.PubMed
203.
Messmer UK, Ankarcrona M, Nicotera P, Brüne B: p53 expression in nitric oxide induced apoptosis. FEBS Lett. 1994, 355: 23-26.PubMed
204.
Rudin CM, Thompson CB: Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med. 1997, 48: 267-281.PubMed
205.
Williams GT, Smith CA: Molecular regulation of apoptosis: genetic controls on cell death. Cell. 1993, 74: 777-779.PubMed
206.
Krammer PH: The CD95(APO-1/Fas)/CD95L system. Toxicol Lett. 1998, 102-103: 131-137.PubMed
207.
Reed JC: Dysregulation of apoptosis in cancer. J Clin Oncol. 1999, 17: 2941-2953.PubMed
208.
Frisch SM, Screaton RA: Anoikis mechanisms. Curr Opin Cell Biol. 2001, 13: 555-562.PubMed
209.
Brune B, Mohr S, Messmer UK: Protein thiol modification and apoptotic cell death as cGMP-independent nitric oxide (NO) signaling pathways. Rev Physiol Biochem Pharmacol. 1996, 127: 1-30.PubMed
210.
Tschugguel W, Pustelnik T, Lass H, Mildner M, Weninger W, Schneeberger C, Jansen B, Tschachler E, Waldhör T, Huber JC, Pehamberger H: Inducible nitric oxide synthase (iNOS) expression may predict distant metastasis in human melanoma. Br J Cancer. 1999, 79: 1609-1612.PubMedCentralPubMed
211.
Ahmed B, Oord Van den JJ: Expression of the inducible isoform of nitric oxide synthase in pigment cell lesions of the skin. Br J Dermatol. 2000, 142: 432-40.PubMed
212.
Ekmekcioglu S, Ellerhorst J, Smid CM, Prieto VG, Munsell M, Buzaid AC, Grimm EA: Inducible nitric oxide synthase and nitrotyrosine in human metastatic melanoma tumors correlate with poor survival. Clin Cancer Res. 2000, 6: 4768-75.PubMed
213.
Ahmed B, Oord Van Den JJ: Expression of the neuronal isoform of nitric oxide synthase (nNOS) and its inhibitor, protein inhibitor of nNOS, in pigment cell lesions of the skin. Br J Dermatol. 1999, 141: 12-19.PubMed
214.
Tang CH, Grimm EA: Depletion of endogenous nitric oxide enhances cisplatin-induced apoptosis in a p53-dependent manner in melanoma cell lines. J Biol Chem. 2004, 279: 288-98.PubMed
215.
Bevona C, Goggins W, Quinn T: Cutaneous melanomas associated with nevi. Arch Dermatol. 2003, 139: 1620-1624.PubMed
216.
Rasheed S, Mao Z, Chan JMC, Chan LS: Is melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells. J Transl Med. 2005, 3: 14-PubMedCentralPubMed
217.
Zabierowski SE, Herlyn M: Melanoma stem cells: the dark seed of melanoma. J Clin Oncol. 2008, 26: 2890-2894.PubMed
Metadata
Title
Main roads to melanoma
Authors
Giuseppe Palmieri
Mariaelena Capone
Maria Libera Ascierto
Giusy Gentilcore
David F Stroncek
Milena Casula
Maria Cristina Sini
Marco Palla
Nicola Mozzillo
Paolo A Ascierto
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-86

Other articles of this Issue 1/2009

Journal of Translational Medicine 1/2009 Go to the issue

Research

Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

Research

Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma

Research

Semi-allogeneic vaccines and tumor-induced immune tolerance

Research

Comparison of the effects of vitamin D products in a psoriasis plaque test and a murine psoriasis xenograft model

Research

High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis

Editorial

Announcing the Tumor Immunology and Biological Cancer Therapy section (edited by iSBTc) of the Journal of Translational Medicine
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits