Abstract
Melanoma is one of the most chemo-resistant cancers and one whose incidence is increasing significantly. Transcription factors are DNA-binding proteins which control gene expression through recognition of specific DNA sequences within target promoter or enhancer regions, either directly or through protein–protein interactions. Many transcription factors have been shown to be oncogenes or tumor suppressors in melanoma. Some of them exhibit activities thought to be common to many cancers, whereas others are thought to be specific to melanoma or melanocytes. Each transcription factor modulates biological activities through a multitude of target genes and in many cases the transcription factor’s activity may be modulated by posttranslational modifications. Unlike enzymes or receptors, only a small fraction of transcription factors have been successfully targeted for therapeutic purposes by small molecules, the most striking examples being nuclear hormone receptors, which are transcription factors that are dependent on binding and activation by drug-like nuclear hormones (e.g., sex steroids, glucocorticoids, etc.). Understanding the regulatory mechanisms and target genes of biologically important transcription factors could lead to the identity of drug-able pathways for melanoma. This is particularly important if the spectrum of currently drug-able oncoproteins is insufficient to produce curative outcomes or if transcriptional mechanisms contribute importantly to resistance from other targeted therapeutic approaches. In this chapter, we select a number of transcription factors that have been implicated in melanoma biology (MITF, CREB, SOX10, PAX3, Snail superfamily, FOXD3, Ets family, Brn2, AP-1, AP-2, LEF/TCF/β-catenin, Notch, NF-kB, SMAD/SKI, STAT3, HIF1A, Tbx-2/3, C-MYC, and p53) and focus on their regulatory mechanisms and biological targets.
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References
Abel EV, Aplin AE (2010) FOXD3 is a mutant B-RAF-regulated inhibitor of G(1)-S progression in melanoma cells. Cancer Res 70:2891–2900
Abel EV, Basile KJ, Kugel CH 3rd, Witkiewicz AK, Le K, Amaravadi RK, Karakousis GC, Xu X, Xu W, Schuchter LM, Lee JB, Ertel A, Fortina P, Aplin AE (2013) Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J Clin Invest 123:2155–2168
Abrahams A, Mowla S, Parker MI, Goding CR, Prince S (2008) UV-mediated regulation of the anti-senescence factor Tbx2. J Biol Chem 283:2223–2230
Alonso-Curbelo D, Riveiro-Falkenbach E, Perez-Guijarro E, Cifdaloz M, Karras P, Osterloh L, Megias D, Canon E, Calvo TG, Olmeda D, Gomez-Lopez G, Grana O, Sanchez-Arevalo Lobo VJ, Pisano DG, Wang HW, Ortiz-Romero P, Tormo D, Hoek K, Rodriguez-Peralto JL, Joyce JA, Soengas MS (2014) RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway. Cancer Cell 26:61–76
Amati B, Littlewood TD, Evan GI, Land H (1993) The c-Myc protein induces cell cycle progression and apoptosis through dimerization with Max. EMBO J 12:5083–5087
Amiri KI, Richmond A (2005) Role of nuclear factor-kappa B in melanoma. Cancer Metastasis Rev 24:301–313
Arozarena I, Sanchez-Laorden B, Packer L, Hidalgo-Carcedo C, Hayward R, Viros A, Sahai E, Marais R (2011) Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cancer Cell 19:45–57
Bailly RA, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J (1994) DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol Cell Biol 14:3230–3241
Balint K, Xiao M, Pinnix CC, Soma A, Veres I, Juhasz I, Brown EJ, Capobianco AJ, Herlyn M, Liu ZJ (2005) Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. J Clin Invest 115:3166–3176
Bar-Eli M (2001) Gene regulation in melanoma progression by the AP-2 transcription factor. Pigment Cell Res 14:78–85
Barr FG, Fitzgerald JC, Ginsberg JP, Vanella ML, Davis RJ, Bennicelli JL (1999) Predominant expression of alternative PAX3 and PAX7 forms in myogenic and neural tumor cell lines. Cancer Res 59:5443–5448
Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A (2000) The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2:84–89
Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, Rimm DL (2003) Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res 63:8103–8107
Bhoumik A, Lopez-Bergami P, Ronai Z (2007) ATF2 on the double - activating transcription factor and DNA damage response protein. Pigment Cell Res 20:498–506
Bhoumik A, Singha N, O’Connell MJ, Ronai ZA (2008) Regulation of TIP60 by ATF2 modulates ATM activation. J Biol Chem 283:17605–17614
Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, Ronai Z (2005) ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol Cell 18:577–587
Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (2000) Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet 9:1907–1917
Boulay JL, Dennefeld C, Alberga A (1987) The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers. Nature 330:395–398
Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE Jr (1999) Stat3 as an oncogene. Cell 98:295–303
Buettner R, Kannan P, Imhof A, Bauer R, Yim SO, Glockshuber R, Van Dyke MW, Tainsky MA (1993) An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2. Mol Cell Biol 13:4174–4185
Buettner R, Mora LB, Jove R (2002) Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 8:945–954
Busca R, Berra E, Gaggioli C, Khaled M, Bille K, Marchetti B, Thyss R, Fitsialos G, Larribere L, Bertolotto C, Virolle T, Barbry P, Pouyssegur J, Ponzio G, Ballotti R (2005) Hypoxia-inducible factor 1{alpha} is a new target of microphthalmia-associated transcription factor (MITF) in melanoma cells. J Cell Biol 170:49–59
Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA (2000) The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2:76–83
Carreira S, Dexter TJ, Yavuzer U, Easty DJ, Goding CR (1998) Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. Mol Cell Biol 18:5099–5108
Carreira S, Liu B, Goding CR (2000) The gene encoding the T-box factor Tbx2 is a target for the microphthalmia-associated transcription factor in melanocytes. J Biol Chem 275:21920–21927
Chen D, Xu W, Bales E, Colmenares C, Conacci-Sorrell M, Ishii S, Stavnezer E, Campisi J, Fisher DE, Ben-Ze’ev A, Medrano EE (2003) SKI activates Wnt/beta-catenin signaling in human melanoma. Cancer Res 63:6626–6634
Cheung M, Briscoe J (2003) Neural crest development is regulated by the transcription factor Sox9. Development 130:5681–5693
Cronin JC, Wunderlich J, Loftus SK, Prickett TD, Wei X, Ridd K, Vemula S, Burrell AS, Agrawal NS, Lin JC, Banister CE, Buckhaults P, Rosenberg SA, Bastian BC, Pavan WJ, Samuels Y (2009) Frequent mutations in the MITF pathway in melanoma. Pigment Cell Melanoma Res 22:435–444
Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL, Igras VE, D’Orazio J, Fung CY, Schanbacher CF, Granter SR, Fisher DE (2007) Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 128:853–864
Davis IJ, Kim JJ, Ozsolak F, Widlund HR, Rozenblatt-Rosen O, Granter SR, Du J, Fletcher JA, Denny CT, Lessnick SL, Linehan WM, Kung AL, Fisher DE (2006) Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers. Cancer Cell 9:473–484
Fan W, Huang X, Chen C, Gray J, Huang T (2004) TBX3 and its isoform TBX3 + 2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast cancer cell lines. Cancer Res 64:5132–5139
Feige E, Yokoyama S, Levy C, Khaled M, Igras V, Lin RJ, Lee S, Widlund HR, Granter SR, Kung AL, Fisher DE (2011) Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF. Proc Natl Acad Sci U S A 108:E924–E933
Ferre-D’Amare AR, Prendergast GC, Ziff EB, Burley SK (1993) Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain. Nature 363:38–45
Fuchs SY, Tappin I, Ronai Z (2000) Stability of the ATF2 transcription factor is regulated by phosphorylation and dephosphorylation. J Biol Chem 275:12560–12564
Fuse N, Yasumoto K, Suzuki H, Takahashi K, Shibahara S (1996) Identification of a melanocyte-type promoter of the microphthalmia-associated transcription factor gene. Biochem Biophys Res Commun 219:702–707
Garraway LA, Weir BA, Zhao X, Widlund H, Beroukhim R, Berger A, Rimm D, Rubin MA, Fisher DE, Meyerson ML, Sellers WR (2005) “Lineage addiction” in human cancer: lessons from integrated genomics. Cold Spring Harb Symp Quant Biol 70:25–34
Gershenwald JE, Sumner W, Calderone T, Wang Z, Huang S, Bar-Eli M (2001) Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo. Oncogene 20:3363–3375
Golan T, Messer AR, Amitai-Lange A, Melamed Z, Ohana R, Bell RE, Kapitansky O, Lerman G, Greenberger S, Khaled M, Amar N, Albrengues J, Gaggioli C, Gonen P, Tabach Y, Sprinzak D, Shalom-Feuerstein R, Levy C (2015) Interactions of melanoma cells with distal keratinocytes trigger metastasis via notch signaling inhibition of MITF. Mol Cell 59:664–676
Goodall J, Carreira S, Denat L, Kobi D, Davidson I, Nuciforo P, Sturm RA, Larue L, Goding CR (2008) Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells. Cancer Res 68:7788–7794
Goulding MD, Chalepakis G, Deutsch U, Erselius JR, Gruss P (1991) Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J 10:1135–1147
Greenwald I (1998) LIN-12/Notch signaling: lessons from worms and flies. Genes Dev 12:1751–1762
Gupta PB, Kuperwasser C, Brunet JP, Ramaswamy S, Kuo WL, Gray JW, Naber SP, Weinberg RA (2005) The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nat Genet 37:1047–1054
Gupta S, Campbell D, Derijard B, Davis RJ (1995) Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267:389–393
Hemesath TJ, Steingrimsson E, McGill G, Hansen MJ, Vaught J, Hodgkinson CA, Arnheiter H, Copeland NG, Jenkins NA, Fisher DE (1994) microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev 8:2770–2780
Herbarth B, Pingault V, Bondurand N, Kuhlbrodt K, Hermans-Borgmeyer I, Puliti A, Lemort N, Goossens M, Wegner M (1998) Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease. Proc Natl Acad Sci U S A 95:5161–5165
Hershey CL, Fisher DE (2005) Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform. Gene 347:73–82
Hilger-Eversheim K, Moser M, Schorle H, Buettner R (2000) Regulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell-cycle control. Gene 260:1–12
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 (2004) Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res 64:5270–5282
Hsieh MJ, Yao YL, Lai IL, Yang WM (2006) Transcriptional repression activity of PAX3 is modulated by competition between corepressor KAP1 and heterochromatin protein 1. Biochem Biophys Res Commun 349:573–581
Jane-Valbuena J, Widlund HR, Perner S, Johnson LA, Dibner AC, Lin WM, Baker AC, Nazarian RM, Vijayendran KG, Sellers WR, Hahn WC, Duncan LM, Rubin MA, Fisher DE, Garraway LA (2010) An oncogenic role for ETV1 in melanoma. Cancer Res 70:2075–2084
Jean D, Gershenwald JE, Huang S, Luca M, Hudson MJ, Tainsky MA, Bar-Eli M (1998) Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor growth and metastasis of human melanoma cells. J Biol Chem 273:16501–16508
Jiao Z, Mollaaghababa R, Pavan WJ, Antonellis A, Green ED, Hornyak TJ (2004) Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase (Dct) and synergistic activation of Dct expression with Mitf. Pigment Cell Res 17:352–362
Kappelmann M, Kuphal S, Meister G, Vardimon L, Bosserhoff AK (2013) MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene 32:2984–2991
Khan MM, Nomura T, Kim H, Kaul SC, Wadhwa R, Shinagawa T, Ichikawa-Iwata E, Zhong S, Pandolfi PP, Ishii S (2001) Role of PML and PML-RARalpha in Mad-mediated transcriptional repression. Mol Cell 7:1233–1243
Kraehn GM, Utikal J, Udart M, Greulich KM, Bezold G, Kaskel P, Leiter U, Peter RU (2001) Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases. Br J Cancer 84(1):72–9.
Kos R, Reedy MV, Johnson RL, Erickson CA (2001) The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos. Development 128:1467–1479
Kubic JD, Little EC, Lui JW, Iizuka T, Lang D (2015a) PAX3 and ETS1 synergistically activate MET expression in melanoma cells. Oncogene 34:4964–4974
Kubic JD, Lui JW, Little EC, Ludvik AE, Konda S, Salgia R, Aplin AE, Lang D (2015b) PAX3 and FOXD3 promote CXCR4 expression in melanoma. J Biol Chem 290:21901–21914
Kumar SM, Yu H, Edwards R, Chen L, Kazianis S, Brafford P, Acs G, Herlyn M, Xu X (2007) Mutant V600E BRAF increases hypoxia inducible factor-1alpha expression in melanoma. Cancer Res 67:3177–3184
Lang D, Lu MM, Huang L, Engleka KA, Zhang M, Chu EY, Lipner S, Skoultchi A, Millar SE, Epstein JA (2005) Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433:884–887
Larribere L, Hilmi C, Khaled M, Gaggioli C, Bille K, Auberger P, Ortonne JP, Ballotti R, Bertolotto C (2005) The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis. Genes Dev 19:1980–1985
Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA (2012) PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell 148:543–555
Levy C, Nechushtan H, Razin E (2002) A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor. J Biol Chem 277:1962–1966
Li WX (2008) Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol 18:545–551
Lin JY, Fisher DE (2007) Melanocyte biology and skin pigmentation. Nature 445:843–850
Liu F, Cao J, Lv J, Dong L, Pier E, Xu GX, Wang RA, Xu Z, Goding C, Cui R (2013) TBX2 expression is regulated by PAX3 in the melanocyte lineage. Pigment Cell Melanoma Res 26:67–77
Liu XY, Lai F, Yan XG, Jiang CC, Guo ST, Wang CY, Croft A, Tseng HY, Wilmott JS, Scolyer RA, Jin L, Zhang XD (2015) RIP1 kinase is an oncogenic driver in melanoma. Cancer Res 75:1736–1748
Lozano G (2007) The oncogenic roles of p53 mutants in mouse models. Curr Opin Genet Dev 17:66–70
Ludwig A, Rehberg S, Wegner M (2004) Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors. FEBS Lett 556:236–244
Luscher B, Mitchell PJ, Williams T, Tjian R (1989) Regulation of transcription factor AP-2 by the morphogen retinoic acid and by second messengers. Genes Dev 3:1507–1517
Maka M, Stolt CC, Wegner M (2005) Identification of Sox8 as a modifier gene in a mouse model of Hirschsprung disease reveals underlying molecular defect. Dev Biol 277:155–169
Mansky KC, Sankar U, Han J, Ostrowski MC (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
Massague J (2000) How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1:169–178
Mauhin V, Lutz Y, Dennefeld C, Alberga A (1993) Definition of the DNA-binding site repertoire for the Drosophila transcription factor SNAIL. Nucleic Acids Res 21:3951–3957
Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275
Medic S, Ziman M (2010) PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas). PLoS One 5:e9977
Miller AJ, Levy C, Davis IJ, Razin E, Fisher DE (2005) Sumoylation of MITF and its related family members TFE3 and TFEB. J Biol Chem 280:146–155
Murakami H, Arnheiter H (2005) Sumoylation modulates transcriptional activity of MITF in a promoter-specific manner. Pigment Cell Res 18:265–277
Murakami M, Tominaga J, Makita R, Uchijima Y, Kurihara Y, Nakagawa O, Asano T, Kurihara H (2006) Transcriptional activity of Pax3 is co-activated by TAZ. Biochem Biophys Res Commun 339:533–539
Myatt SS, Lam EW (2007) The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 7:847–859
Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J 16:5353–5362
Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R, Yu H (1999) Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res 59:5059–5063
Niu G, Shain KH, Huang M, Ravi R, Bedi A, Dalton WS, Jove R, Yu H (2001) Overexpression of a dominant-negative signal transducer and activator of transcription 3 variant in tumor cells leads to production of soluble factors that induce apoptosis and cell cycle arrest. Cancer Res 61:3276–3280
Ouchida M, Ohno T, Fujimura Y, Rao VN, Reddy ES (1995) Loss of tumorigenicity of Ewing’s sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene 11:1049–1054
Ouwens DM, de Ruiter ND, van der Zon GC, Carter AP, Schouten J, van der Burgt C, Kooistra K, Bos JL, Maassen JA, van Dam H (2002) Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38. EMBO J 21:3782–3793
Passeron T, Valencia JC, Bertolotto C, Hoashi T, Le Pape E, Takahashi K, Ballotti R, Hearing VJ (2007) SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation. Proc Natl Acad Sci U S A 104:13984–13989
Peirano RI, Wegner M (2000) The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences. Nucleic Acids Res 28:3047–3055
Perkins ND (2012) The diverse and complex roles of NF-kappaB subunits in cancer. Nat Rev Cancer 12:121–132
Pierrat MJ, Marsaud V, Mauviel A, Javelaud D (2012) Expression of microphthalmia-associated transcription factor (MITF), which is critical for melanoma progression, is inhibited by both transcription factor GLI2 and transforming growth factor-beta. J Biol Chem 287:17996–18004
Plummer RS, Shea CR, Nelson M, Powell SK, Freeman DM, Dan CP, Lang D (2008) PAX3 expression in primary melanomas and nevi. Mod Pathol 21:525–530
Polsky D, Bastian BC, Hazan C, Melzer K, Pack J, Houghton A, Busam K, Cordon-Cardo C, Osman I (2001) HDM2 protein overexpression, but not gene amplification, is related to tumorigenesis of cutaneous melanoma. Cancer Res 61:7642–7646
Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9:265–273
Poser I, Dominguez D, de Herreros AG, Varnai A, Buettner R, Bosserhoff AK (2001) Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem 276:24661–24666
Price ER, Horstmann MA, Wells AG, Weilbaecher KN, Takemoto CM, Landis MW, Fisher DE (1998) alpha-Melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome. J Biol Chem 273:33042–33047
Pruijn GJ, van Driel W, van der Vliet PC (1986) Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication. Nature 322:656–659
Pruijn GJ, van Driel W, van Miltenburg RT, van der Vliet PC (1987) Promoter and enhancer elements containing a conserved sequence motif are recognized by nuclear factor III, a protein stimulating adenovirus DNA replication. EMBO J 6:3771–3778
Radtke F, Raj K (2003) The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer 3:756–767
Reed JA, Bales E, Xu W, Okan NA, Bandyopadhyay D, Medrano EE (2001) Cytoplasmic localization of the oncogenic protein Ski in human cutaneous melanomas in vivo: functional implications for transforming growth factor beta signaling. Cancer Res 61:8074–8078
Reynisdottir I, Polyak K, Iavarone A, Massague J (1995) Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev 9:1831–1845
Riley T, Sontag E, Chen P, Levine A (2008) Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 9:402–412
Sanchez-Martin M, Rodriguez-Garcia A, Perez-Losada J, Sagrera A, Read AP, Sanchez-Garcia I (2002) SLUG (SNAI2) deletions in patients with Waardenburg disease. Hum Mol Genet 11:3231–3236
Schindler C, Shuai K, Prezioso VR, Darnell JE Jr (1992) Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257:809–813
Scholl FA, Kamarashev J, Murmann OV, Geertsen R, Dummer R, Schafer BW (2001) PAX3 is expressed in human melanomas and contributes to tumor cell survival. Cancer Res 61:823–826
Sen R, Baltimore D (1986) Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 47:921–928
Sharrocks AD (2001) The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2:827–837
Shuai K, Schindler C, Prezioso VR, Darnell JE Jr (1992) Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 258:1808–1812
Sinclair CS, Adem C, Naderi A, Soderberg CL, Johnson M, Wu K, Wadum L, Couch VL, Sellers TA, Schaid D, Slezak J, Fredericksen Z, Ingle JN, Hartmann L, Jenkins RB, Couch FJ (2002) TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors. Cancer Res 62:3587–3591
Smit DJ, Smith AG, Parsons PG, Muscat GE, Sturm RA (2000) Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors. Eur J Biochem 267:6413–6422
Soullier S, Jay P, Poulat F, Vanacker JM, Berta P, Laudet V (1999) Diversification pattern of the HMG and SOX family members during evolution. J Mol Evol 48:517–527
Southard-Smith EM, Kos L, Pavan WJ (1998) Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet 18:60–64
Spranger S, Bao R, Gajewski TF (2015) Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 523:231–235
Stavnezer E, Gerhard DS, Binari RC, Balazs I (1981) Generation of transforming viruses in cultures of chicken fibroblasts infected with an avian leukosis virus. J Virol 39:920–934
Sturm RA, Herr W (1988) The POU domain is a bipartite DNA-binding structure. Nature 336:601–604
Sun C, Wang L, Huang S, Heynen GJ, Prahallad A, Robert C, Haanen J, Blank C, Wesseling J, Willems SM, Zecchin D, Hobor S, Bajpe PK, Lieftink C, Mateus C, Vagner S, Grernrum W, Hofland I, Schlicker A, Wessels LF, Beijersbergen RL, Bardelli A, Di Nicolantonio F, Eggermont AM, Bernards R (2014) Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 508:118–122
Takeda K, Yasumoto K, Takada R, Takada S, Watanabe K, Udono T, Saito H, Takahashi K, Shibahara S (2000) Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J Biol Chem 275:14013–14016
Tassabehji M, Newton VE, Read AP (1994) Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. Nat Genet 8:251–255
Tassabehji M, Read AP, Newton VE, Patton M, Gruss P, Harris R, Strachan T (1993) Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2. Nat Genet 3:26–30
Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S, Leder P (1982) Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A 79:7837–7841
Thomas AJ, Erickson CA (2009) FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism. Development 136:1849–1858
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310:644–648
Vance KW, Carreira S, Brosch G, Goding CR (2005) Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. Cancer Res 65:2260–2268
Verfaillie A, Imrichova H, Atak ZK, Dewaele M, Rambow F, Hulselmans G, Christiaens V, Svetlichnyy D, Luciani F, Van den Mooter L, Claerhout S, Fiers M, Journe F, Ghanem GE, Herrmann C, Halder G, Marine JC, Aerts S (2015) Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state. Nat Commun 6:6683
Vogt PK (2002) Fortuitous convergences: the beginnings of JUN. Nat Rev Cancer 2:465–469
Volkenandt M, Schlegel U, Nanus DM, Albino AP (1991) Mutational analysis of the human p53 gene in malignant melanoma. Pigment Cell Res 4:35–40
Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, Bhattacharya R, Gabrilovich D, Heller R, Coppola D, Dalton W, Jove R, Pardoll D, Yu H (2004) Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 10:48–54
Warner BJ, Blain SW, Seoane J, Massague J (1999) Myc downregulation by transforming growth factor beta required for activation of the p15(Ink4b) G(1) arrest pathway. Mol Cell Biol 19:5913–5922
Weeraratna AT (2005) A Wnt-er wonderland – the complexity of Wnt signaling in melanoma. Cancer Metastasis Rev 24:237–250
Wegner M (2005) Secrets to a healthy Sox life: lessons for melanocytes. Pigment Cell Res 18:74–85
Weilbaecher KN, Motyckova G, Huber WE, Takemoto CM, Hemesath TJ, Xu Y, Hershey CL, Dowland NR, Wells AG, Fisher DE (2001) Linkage of M-CSF signaling to Mitf, TFE3, and the osteoclast defect in Mitf(mi/mi) mice. Mol Cell 8:749–758
Weiss MB, Abel EV, Dadpey N, Aplin AE (2014) FOXD3 modulates migration through direct transcriptional repression of TWIST1 in melanoma. Mol Cancer Res 12:1314–1323
Widlund HR, Horstmann MA, Price ER, Cui J, Lessnick SL, Wu M, He X, Fisher DE (2002) Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J Cell Biol 158:1079–1087
Wilson A, Radtke F (2006) Multiple functions of Notch signaling in self-renewing organs and cancer. FEBS Lett 580:2860–2868
Wu M, Hemesath TJ, Takemoto CM, Horstmann MA, Wells AG, Price ER, Fisher DZ, Fisher DE (2000) c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev 14:301–312
Xie S, Price JE, Luca M, Jean D, Ronai Z, Bar-Eli M (1997) Dominant-negative CREB inhibits tumor growth and metastasis of human melanoma cells. Oncogene 15:2069–2075
Xie TX, Wei D, Liu M, Gao AC, Ali-Osman F, Sawaya R, Huang S (2004) Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 23:3550–3560
Xu Q, Briggs J, Park S, Niu G, Kortylewski M, Zhang S, Gritsko T, Turkson J, Kay H, Semenza GL, Cheng JQ, Jove R, Yu H (2005) Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 24:5552–5560
Yamaguchi Y, Hearing VJ (2009) Physiological factors that regulate skin pigmentation. Biofactors 35:193–199
Yang J, Richmond A (2001) Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Cancer Res 61:4901–4909
Yang J, Splittgerber R, Yull FE, Kantrow S, Ayers GD, Karin M, Richmond A (2010) Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest 120:2563–2574
Yasumoto K, Yokoyama K, Shibata K, Tomita Y, Shibahara S (1994) Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene. Mol Cell Biol 14:8058–8070
Yokoyama S, Feige E, Poling LL, Levy C, Widlund HR, Khaled M, Kung AL, Fisher DE (2008) Pharmacologic suppression of MITF expression via HDAC inhibitors in the melanocyte lineage. Pigment Cell Melanoma Res 21:457–463
Yokoyama S, Woods SL, Boyle GM, Aoude LG, MacGregor S, Zismann V, Gartside M, Cust AE, Haq R, Harland M, Taylor JC, Duffy DL, Holohan K, Dutton-Regester K, Palmer JM, Bonazzi V, Stark MS, Symmons J, Law MH, Schmidt C, Lanagan C, O’Connor L, Holland EA, Schmid H, Maskiell JA, Jetann J, Ferguson M, Jenkins MA, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Whiteman DC, Pharoah PD, Easton DF, Dunning AM, Newton-Bishop JA, Montgomery GW, Martin NG, Mann GJ, Bishop DT, Tsao H, Trent JM, Fisher DE, Hayward NK, Brown KM (2011) A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 480:99–103
Yuan H, Corbi N, Basilico C, Dailey L (1995) Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev 9:2635–2645
Zhu S, Wurdak H, Wang Y, Galkin A, Tao H, Li J, Lyssiotis CA, Yan F, Tu BP, Miraglia L, Walker J, Sun F, Orth A, Schultz PG, Wu X (2009) A genomic screen identifies TYRO3 as a MITF regulator in melanoma. Proc Natl Acad Sci U S A 106:17025–17030
Zhuang D, Mannava S, Grachtchouk V, Tang WH, Patil S, Wawrzyniak JA, Berman AE, Giordano TJ, Prochownik EV, Soengas MS, Nikiforov MA (2008) C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene 27:6623–6634
Zilberberg A, Yaniv A, Gazit A (2004) The low density lipoprotein receptor-1, LRP1, interacts with the human frizzled-1 (HFz1) and down-regulates the canonical Wnt signaling pathway. J Biol Chem 279:17535–17542
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Yokoyama, S., Fisher, D.E. (2017). Transcriptional Regulation in Melanoma. In: Bosserhoff, A. (eds) Melanoma Development. Springer, Cham. https://doi.org/10.1007/978-3-319-41319-8_5
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