NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

Takashi Nishina, Noritaka Yamaguchi, Jin Gohda, Kentaro Senba, Jun ichiro Inoue

    研究成果: Article

    29 引用 (Scopus)

    抄録

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

    元の言語English
    ページ(範囲)96-101
    ページ数6
    ジャーナルBiochemical and Biophysical Research Communications
    388
    発行部数1
    DOI
    出版物ステータスPublished - 2009 10 9

    Fingerprint

    Pancreatic Neoplasms
    Phosphotransferases
    Chemical activation
    Cells
    Cell proliferation
    Fractionation
    Cell Nucleus Active Transport
    Small Interfering RNA
    Neoplasms
    Cell Proliferation
    Processing

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology
    • Molecular Biology

    これを引用

    NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells. / Nishina, Takashi; Yamaguchi, Noritaka; Gohda, Jin; Senba, Kentaro; Inoue, Jun ichiro.

    :: Biochemical and Biophysical Research Communications, 巻 388, 番号 1, 09.10.2009, p. 96-101.

    研究成果: Article

    @article{9f0b3ccd31664ab2b13c43d079142b5f,
    title = "NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells",
    abstract = "Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.",
    keywords = "Alternative pathway, IKKα, NIK, Pancreatic cancer, RelB",
    author = "Takashi Nishina and Noritaka Yamaguchi and Jin Gohda and Kentaro Senba and Inoue, {Jun ichiro}",
    year = "2009",
    month = "10",
    day = "9",
    doi = "10.1016/j.bbrc.2009.07.125",
    language = "English",
    volume = "388",
    pages = "96--101",
    journal = "Biochemical and Biophysical Research Communications",
    issn = "0006-291X",
    publisher = "Academic Press Inc.",
    number = "1",

    }

    TY - JOUR

    T1 - NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

    AU - Nishina, Takashi

    AU - Yamaguchi, Noritaka

    AU - Gohda, Jin

    AU - Senba, Kentaro

    AU - Inoue, Jun ichiro

    PY - 2009/10/9

    Y1 - 2009/10/9

    N2 - Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

    AB - Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

    KW - Alternative pathway

    KW - IKKα

    KW - NIK

    KW - Pancreatic cancer

    KW - RelB

    UR - http://www.scopus.com/inward/record.url?scp=68949097479&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=68949097479&partnerID=8YFLogxK

    U2 - 10.1016/j.bbrc.2009.07.125

    DO - 10.1016/j.bbrc.2009.07.125

    M3 - Article

    VL - 388

    SP - 96

    EP - 101

    JO - Biochemical and Biophysical Research Communications

    JF - Biochemical and Biophysical Research Communications

    SN - 0006-291X

    IS - 1

    ER -