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

Author

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  • Mizuki Yamamoto

    (Institute of Medical Science, University of Tokyo, Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan
    Waseda University, Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan)

  • Yuu Taguchi

    (Institute of Medical Science, University of Tokyo, Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan)

  • Taku Ito-Kureha

    (Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan)

  • Kentaro Semba

    (Waseda University, Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan)

  • Noritaka Yamaguchi

    (Graduate School of Pharmaceutical Sciences, Chiba University)

  • Jun-ichiro Inoue

    (Institute of Medical Science, University of Tokyo, Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan)

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.

Suggested Citation

  • Mizuki Yamamoto & Yuu Taguchi & Taku Ito-Kureha & Kentaro Semba & Noritaka Yamaguchi & Jun-ichiro Inoue, 2013. "NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype," Nature Communications, Nature, vol. 4(1), pages 1-13, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3299
    DOI: 10.1038/ncomms3299
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