Ectopic Ikaros Expression Positively Correlates With Lung Cancer Progression

Authors

  • Zhenfa Zhang,

    1. Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
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    • Zhenfa Zhang and Zhao Xu contributed equally to this work.

  • Zhao Xu,

    1. Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
    2. Department of Immunology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
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    • Zhenfa Zhang and Zhao Xu contributed equally to this work.

  • Xiaoyang Wang,

    1. Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
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  • Hao Wang,

    1. Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
    2. Department of Immunology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
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  • Zhi Yao,

    1. Department of Immunology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
    2. Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin, China
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  • Yanchao Mu,

    1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
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  • Zhenyi Ma,

    Corresponding author
    • Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
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  • Zhe Liu

    Corresponding author
    1. Department of Immunology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
    2. Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin, China
    • Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
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Correspondence to: Zhe Liu, Tianjin Key Laboratory of Medical Epigenetics, Department of Immunology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. E-mail: zheliu@tmu.edu.cn or Zhenyi Ma, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. E-mail: zhyma@tmu.edu.cn

ABSTRACT

Ikaros, encoded by the IKZF1 gene, is a pivotal transcription factor whose expression and utilization is dynamically altered during hematopoietic development. However, the molecular mechanisms controlling the transcription of the IKZF1 gene are unclear in lung cancer cell lines. Here we show the role of Ikaros in a cohort of grade IIIA lung cancer patients, with particular emphasis on its relationship with clinical outcomes and expression levels. The expression levels of Ikaros were positively correlated with the prognosis in the lung cancer patients. We also demonstrated that Ikaros expression is ectopically activated in a panel of lung cancer cell lines primarily through demethylation of its promoter. Moreover, gain-of-function experiments revealed that Ikaros inhibits migration and invasion of lung cancer cells in vitro. Our results thus shed light on how Ikaros can act as a lineage competency factor to facilitate lung cancer progression. Anat Rec, 296:907–913, 2013. © 2013 Wiley Periodicals, Inc.

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