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dc.contributor.authorDyberg, Cecilia
dc.contributor.authorFransson, Susanne
dc.contributor.authorAndonova, Teodora
dc.contributor.authorSveinbjørnsson, Baldur
dc.contributor.authorLannerholm-Palm, Jessika
dc.contributor.authorOlsen, Thale Kristin
dc.contributor.authorForsberg, David
dc.contributor.authorHerlenius, Eric
dc.contributor.authorMartinsson, Tommy
dc.contributor.authorBrodin, Bertha
dc.contributor.authorKogner, Per
dc.contributor.authorJohnsen, John Inge
dc.contributor.authorWickström, Malin
dc.date.accessioned2018-04-04T07:28:04Z
dc.date.available2018-04-04T07:28:04Z
dc.date.issued2017-07-24
dc.description.abstractNeuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN-driven neuroblastoma growth in TH-MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.en_US
dc.description.sponsorshipThe Swedish Childhood Cancer Foundation, Swedish Cancer Foundation, Swedish Research Council, Eva och Oscars Ahréns Research Foundation, Magnus Bergvall Foundation, Mary Béve Foundation, Märta and Gunnar V. Philipson Foundation, AnnaBrita and Bo Castegren Memorial Foundation, Sigurd and Elsa Goljes Memorial Foundation, Swedish Foundation for Strategic Research (www.nnbcr.se), Karolinska Institutet, Stockholm County Council, Cancer Research Foundations of Radiumhemmeten_US
dc.descriptionSource at: <a href=http://doi.org/10.1073/pnas.1706011114> http://doi.org/10.1073/pnas.1706011114 </a>en_US
dc.identifier.citationDyberg, C., Fransson, S., Andonova, T., Sveinbjørnsson, B., Lannerholm-Palm, J., Olsen, T. K., Forsberg, D. ... Wickström, M. (2017). Rho-associated kinase is a therapeutic target in neuroblastoma. Proceedings of the National Academy of Sciences of the United States of America, 114(32), E6603-E6612. http://doi.org/10.1073/pnas.1706011114en_US
dc.identifier.cristinIDFRIDAID 1543259
dc.identifier.doi10.1073/pnas.1706011114
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttps://hdl.handle.net/10037/12465
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Infeksjonsmedisin: 776en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Communicable diseases: 776en_US
dc.titleRho-associated kinase is a therapeutic target in neuroblastomaen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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