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 thatALK expression was significantly high in NBL clinical samples with amplifiedMYCN (n5126,P
, 0.01) and in developing tumors ofMYCN-transgenic mice. Indeed, promoter analysis revealed thatALK
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.