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

Md Kamrul Hasan, Asmaa Nafady, Atsushi Takatori, Satoshi Kishida, Miki Ohira, Yusuke Suenaga, Shamim Hossain, Jesmin Akter, Atsushi Ogura, Yohko Nakamura, Kenji Kadomatsu, Akira Nakagawara

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35 Citations (Scopus)

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.

Original languageEnglish
Article number3450
JournalScientific reports
Volume3
DOIs
Publication statusPublished - Dec 20 2013

All Science Journal Classification (ASJC) codes

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    Hasan, M. K., Nafady, A., Takatori, A., Kishida, S., Ohira, M., Suenaga, Y., Hossain, S., Akter, J., Ogura, A., Nakamura, Y., Kadomatsu, K., & Nakagawara, A. (2013). ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma. Scientific reports, 3, [3450]. https://doi.org/10.1038/srep03450