NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype

Mizuki Yamamoto, Yuu Taguchi, Taku Ito-Kureha, Kentaro Senba, Noritaka Yamaguchi, Jun Ichiro Inoue

    Research output: Contribution to journalArticle

    95 Citations (Scopus)

    Abstract

    Patients with triple-negative breast cancer display the highest rates of early relapse of all patients with breast cancer. The basal-like subtype, a subgroup of triple-negative breast cancer, exhibits high levels of constitutively active NF-κB signalling. Here we show that NF-κB activation, induced by inflammatory cytokines or by epigenetically dysregulated NIK expression, cell-autonomously upregulates JAG1 expression in non-cancer stem cells. This upregulation stimulates NOTCH signalling in cancer stem cells in trans, leading to an expansion of cancer stem cell populations. Among breast cancers, the NF-κB-dependent induction of JAG1 and the NOTCH-dependent expansion of the cancer stem cell population occur only in the basal-like subtype. Collectively, our results indicate that NF-κB has a non-cell-autonomous role in regulating cancer stem cell populations by forming intratumoural microenvironments composed of JAG1-expressing non-cancer stem cells with a basal-like subtype.

    Original languageEnglish
    Article number2299
    JournalNature Communications
    Volume4
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Neoplastic Stem Cells
    stem cells
    Stem cells
    breast
    cancer
    Triple Negative Breast Neoplasms
    Breast Neoplasms
    Population
    Up-Regulation
    Stem Cells
    Cytokines
    Recurrence
    expansion
    subgroups
    Chemical activation
    induction
    activation
    cells

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Chemistry(all)
    • Physics and Astronomy(all)

    Cite this

    NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype. / Yamamoto, Mizuki; Taguchi, Yuu; Ito-Kureha, Taku; Senba, Kentaro; Yamaguchi, Noritaka; Inoue, Jun Ichiro.

    In: Nature Communications, Vol. 4, 2299, 2013.

    Research output: Contribution to journalArticle

    Yamamoto, Mizuki ; Taguchi, Yuu ; Ito-Kureha, Taku ; Senba, Kentaro ; Yamaguchi, Noritaka ; Inoue, Jun Ichiro. / NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype. In: Nature Communications. 2013 ; Vol. 4.
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    AU - Yamaguchi, Noritaka

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