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

doi:10.1038/srep03450

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

Research output: Contribution to journal › Article › peer-review

77 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 language	English
Article number	3450
Journal	Scientific reports
Volume	3
DOIs	https://doi.org/10.1038/srep03450
Publication status	Published - Dec 20 2013
Externally published	Yes

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@article{f5051a9bc0b044778cf69120f1e6d3a9,

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.",

author = "Hasan, \{Md Kamrul\} and Asmaa Nafady and Atsushi Takatori and Satoshi Kishida and Miki Ohira and Yusuke Suenaga and Shamim Hossain and Jesmin Akter and Atsushi Ogura and Yohko Nakamura and Kenji Kadomatsu and Akira Nakagawara",

note = "Funding Information: We are grateful to Dr. N. Koshikawa and Mr. M. A. Rahman (Chiba Cancer Center Research Institute, Japan) for their excellent technical advice and to Dr. A. Nakazawa (National Center for Child Health and Development, Japan) for useful discussions. We also thank Drs. M. Atwa, H. G. A. El\_Azeem and E. El\_Gezawy (Assiut University, Egypt) for their important suggestions. This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare for the Third Term Comprehensive Control Research for Cancer (A. Nakagawara), a Grant-in-Aid for JSPS KAKENHI Grant Number 24249061 and 21390317 (A. Nakagawara), Takeda Science Foundation (A. Nakagawara) and grant-in-aids from the National Cancer Center Research and Development Fund, Japan (K. Kadomatsu and A. Nakagawara).",

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doi = "10.1038/srep03450",

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T1 - ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma

AU - Hasan, Md Kamrul

AU - Nafady, Asmaa

AU - Takatori, Atsushi

AU - Kishida, Satoshi

AU - Ohira, Miki

AU - Suenaga, Yusuke

AU - Hossain, Shamim

AU - Akter, Jesmin

AU - Ogura, Atsushi

AU - Nakamura, Yohko

AU - Kadomatsu, Kenji

AU - Nakagawara, Akira

N1 - Funding Information: We are grateful to Dr. N. Koshikawa and Mr. M. A. Rahman (Chiba Cancer Center Research Institute, Japan) for their excellent technical advice and to Dr. A. Nakazawa (National Center for Child Health and Development, Japan) for useful discussions. We also thank Drs. M. Atwa, H. G. A. El_Azeem and E. El_Gezawy (Assiut University, Egypt) for their important suggestions. This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare for the Third Term Comprehensive Control Research for Cancer (A. Nakagawara), a Grant-in-Aid for JSPS KAKENHI Grant Number 24249061 and 21390317 (A. Nakagawara), Takeda Science Foundation (A. Nakagawara) and grant-in-aids from the National Cancer Center Research and Development Fund, Japan (K. Kadomatsu and A. Nakagawara).

PY - 2013/12/20

Y1 - 2013/12/20

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/84890949034#tab=citedBy

U2 - 10.1038/srep03450

DO - 10.1038/srep03450

M3 - Article

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AN - SCOPUS:84890949034

SN - 2045-2322

VL - 3

JO - Scientific reports

JF - Scientific reports

M1 - 3450

ER -

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

Abstract

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