Umapathy, GaneshGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Göteborg, Sweden
(författare)
The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma
Artikel/kapitelEngelska2014
Förlag, utgivningsår, omfång ...
American Association for the Advancement of Science (AAAS),2014
Anaplastic lymphoma kinase (ALK) is an important molecular target in neuroblastoma. Although tyrosine kinase inhibitors abrogating ALK activity are currently in clinical use for the treatment of ALK-positive (ALK(+)) disease, monotherapy with ALK tyrosine kinase inhibitors may not be an adequate solution for ALK(+) neuroblastoma patients. Increased expression of the gene encoding the transcription factor MYCN is common in neuroblastomas and correlates with poor prognosis. We found that the kinase ERK5 [also known as big mitogen-activated protein kinase (MAPK) 1 (BMK1)] is activated by ALK through a pathway mediated by phosphoinositide 3-kinase (PI3K), AKT, MAPK kinase kinase 3 (MEKK3), and MAPK kinase 5 (MEK5). ALK-induced transcription of MYCN and stimulation of cell proliferation required ERK5. Pharmacological or RNA interference-mediated inhibition of ERK5 suppressed the proliferation of neuroblastoma cells in culture and enhanced the antitumor efficacy of the ALK inhibitor crizotinib in both cells and xenograft models. Together, our results indicate that ERK5 mediates ALK-induced transcription of MYCN and proliferation of neuroblastoma, suggesting that targeting both ERK5 and ALK may be beneficial in neuroblastoma patients.
Ruuth, KristinaUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)krru0001
(författare)
Schönherr, ChristinaUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)chsc0002
(författare)
Palmer, Ruth H.,1970Umeå universitet,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Institutionen för molekylärbiologi (Medicinska fakulteten),Göteborg, Sweden(Swepub:umu)rupa0001
(författare)
Hallberg, Bengt,1956Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Göteborg, Sweden(Swepub:gu)xhalbe
(författare)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
(creator_code:org_t)
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Ingår i:Science Signaling: American Association for the Advancement of Science (AAAS)7:3491945-08771937-9145