ALK-stimulated MYCN gene expression

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R-HSA-9725315
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Reaction [BlackBoxEvent]
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Homo sapiens
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MYCN gene expression is stimulated downstream of wild-type and activated ALK signaling in neuronal and neuroblastoma cell lines as well as in murine neuroblastoma models (Schonherr et al, 2012; Montavon et al, 2014). MYCN and ALK are both located on chromosome 2, which is subject to amplifications in neuroblastoma, and ALK and MYCN are both implicated as contributing to neuroblastoma progression (Mosse et al, 2008; Caren et al, 2008; Hasan et al, 2012; De Brouwer et al, 2010; Montavon et al, 2012; Zhu et al, 2012). Abrogation of ALK activity with protein tyrosine kinase inhibitors or with anti-siRNA against ALK decreases MYCN transcript and protein levels, but the direct mechanisms for ALK-dependent MYCN gene expression have not been identified (Schonherr et al, 2012; Hallberg and Palmer, 2013; Roskoski, 2013).

Literature References
PubMed ID Title Journal Year
18724359 Identification of ALK as a major familial neuroblastoma predisposition gene

Hakonarson, H, Kim, C, Speleman, F, Laureys, G, Mossé, YP, Hou, C, Schork, NJ, Maris, JM, Tonini, GP, Devoto, M, Attiyeh, EF, Rappaport, E, Laudenslager, M, Cole, KA, Wood, A, Lynch, JE, Sennett, R, Laquaglia, MJ, Longo, L, Torkamani, A, Perri, P, Brodeur, GM

Nature 2008
24356251 ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma

Nafady, A, Ohira, M, Nakamura, Y, Akter, J, Hossain, S, Hasan, MK, Ogura, A, Takatori, A, Nakagawara, A, Kadomatsu, K, Suenaga, Y, Kishida, S

Sci Rep 2013
24947326 Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells

Sommer, L, Delattre, O, Jauquier, N, Coulon, A, Peuchmaur, M, Bourloud, KB, Flahaut, M, Yan, P, Mühlethaler-Mottet, A, Janoueix-Lerosey, I, Joseph, JM, Montavon, G, Gross, N

Oncotarget 2014
22439933 Activated ALK collaborates with MYCN in neuroblastoma pathogenesis

George, RE, Rodig, SJ, Shin, J, Zhu, S, Helman, D, Kanki, JP, Stewart, RA, Wang, W, Lee, JS, Look, AT, Feng, H, Neuberg, DS, Guo, F, Kutok, JL, Pérez-Atayde, AR

Cancer Cell 2012
20719933 Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification

Laureys, G, Cools, J, Eggert, A, Caron, H, Renard, M, Lakeman, A, Porcu, M, Van Maerken, T, De Brouwer, S, Westerhout, EM, Schulte, JH, Janoueix-Lerosey, I, Vandesompele, J, Ohira, M, Speleman, F, De Preter, K, Vermeulen, J, Versteeg, R, Zabrocki, P, Kumps, C, Nakagawara, A, Hoebeeck, J, Van Roy, N, Schramm, A, Noguera, R, Beiske, K, Delattre, O, De Paepe, A, Kogner, P, Martinsson, T, Van den Broecke, C

Clin Cancer Res 2010
18990089 High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours

Abel, F, Carén, H, Kogner, P, Martinsson, T

Biochem J 2008
23201355 Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition

Roskoski, R

Pharmacol. Res. 2013
22286764 Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells

Wang, CL, Hallberg, B, Kamaraj, S, Martinsson, T, Palmer, RH, Yang, HL, Ruuth, K, Combaret, V, Christensen, JG, Schönherr, C, Djos, A

Oncogene 2012
24060861 Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology

Palmer, RH, Hallberg, B

Nat. Rev. Cancer 2013
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