title: ALK pERKs up MYCN in neuroblastoma.
abstract: The gene expressing the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) is mutated and aberrantly expressed in several cancers. The clinical efficacy of the ALK inhibitor, crizotinib, lags behind expectations for treating MYCN-amplified, ALK-mutant neuroblastoma, a deadly childhood cancer. In this issue of Science Signaling, Umapathy et al. identify the kinase extracellular signal-regulated kinase 5 (ERK5) as a central mediator that enables ALK to boost MYCN expression, and they show that inhibiting ERK5 in concert with ALK reduced neuroblastoma cell viability in vitro and in xenograft tumor models. This report has important clinical implications for the treatment of patients with neuroblastoma or other tumors that overexpress MYC(N) and harbor ALK mutations, such as non-small-cell lung cancer.
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), Partner Site Essen/Duesseldorf, 45122 Essen, Germany. Department of Translational Neuro-Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstr.55, 45122 Essen, Germany. German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Centre for Medical Biotechnology, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Lindner
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, 45122 Essen, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Henssen
authors.affiliation: Department of Pediatric Oncology, Hematology and Blood and Marrow Transplantation, Charité University Medicine, Campus Virchow Klinikum, 13353 Berlin, Germany.
authors.forename: Kathy
authors.initials: K
authors.lastname: Astrahantseff
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, 45122 Essen, Germany. German Cancer Consortium (DKTK), Partner Site Essen/Duesseldorf, 45122 Essen, Germany. Department of Translational Neuro-Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstr.55, 45122 Essen, Germany. German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Centre for Medical Biotechnology, University Duisburg-Essen, 45122 Essen, Germany. johannes.schulte@uk-essen.de.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D048054:Mitogen-Activated Protein Kinase 7