ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.
ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.
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DOI：
10.1038/srep03450
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发表时间：
2013-12-20
影响因子：
4.6
通讯作者：
Nakagawara, Akira
中科院分区：
文献类型：
--
作者：
Hasan, Md. Kamrul;Nafady, Asmaa;Takatori, Atsushi;Kishida, Satoshi;Ohira, Miki;Suenaga, Yusuke;Hossain, Shamim;Akter, Jesmin;Ogura, Atsushi;Nakamura, Yohko;Kadomatsu, Kenji;Nakagawara, Akira
人间变性淋巴瘤激酶(ALK)是一种在NBLS中发生突变或扩增的癌基因。为了更好地了解与ALK相关的分子事件在NBL发病机制中的作用，有必要阐明ALK基因在NBL进展中的作用。在目前的研究中，我们发现在扩增了MYCN的NBL临床样本(n=126，P<；0.01)和MYCN转基因小鼠发育中的肿瘤中ALK的表达显著升高。事实上，启动子分析表明，ALK是MYCN的直接转录靶点。ALK的过表达和下调证实了其在细胞增殖、迁移和侵袭中的作用。此外，用碱性磷酸酶抑制剂TAE-684治疗，有效地抑制了MYCN扩增细胞中的这种生物学效应和小鼠异种移植瘤的生长。我们目前的发现探索了对ALK的基本理解，以便通过靶向ALK进行侵袭性NBL治疗来开发新的治疗工具。
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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影响因子：
3.7
作者：
Bachetti, Tiziana;Di Paolo, Daniela;Perri, Patrizia
通讯作者：
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通讯作者：
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作者：
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