title: ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.
abstract: Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is mutated or amplified in NBLs. To obtain a better understanding of the molecular events associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. In the present study, we found that ALK expression was significantly high in NBL clinical samples with amplified MYCN (n = 126, P < 0.01) and in developing tumors of MYCN-transgenic mice. Indeed, promoter analysis revealed that ALK is a direct transcriptional target of MYCN. Overexpression and knockdown of ALK demonstrated its function in cell proliferation, migration and invasion. Moreover, treatment with an ALK inhibitor, TAE-684, efficiently suppressed such biological effects in MYCN amplified cells and tumor growth of the xenograft in mice. Our present findings explore the fundamental understanding of ALK in order to develop novel therapeutic tools by targeting ALK for aggressive NBL treatment.
authors.affiliation: 1] Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan [2] Department of Molecular Biology and Oncology, Chiba University Graduate School of Medicine, Chiba, Japan [3].
authors.forename: Md Kamrul
authors.initials: MK
authors.lastname: Hasan
authors.affiliation: 1] Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan [2] Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt; Department of Molecular Biology and Oncology, Chiba University Graduate School of Medicine, Chiba, Japan [3].
authors.forename: Asmaa
authors.initials: A
authors.lastname: Nafady
authors.affiliation: Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takatori
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishida
authors.affiliation: Division of Cancer Genomics, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suenaga
authors.affiliation: Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan.
authors.forename: Shamim
authors.initials: S
authors.lastname: Hossain
authors.affiliation: Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan.
authors.forename: Jesmin
authors.initials: J
authors.lastname: Akter
authors.affiliation: Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogura
authors.affiliation: Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
authors.affiliation: 1] Division of Biochemistry & Innovative Cancer Therapeutics, and Children's Cancer Research Center, Chiba Cancer Center, Chiba, Japan [2] Department of Molecular Biology and Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051379:Mice; D000071447:N-Myc Proto-Oncogene Protein; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases