Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth

Taku Ito-Kureha, Naohiko Koshikawa, Mizuki Yamamoto, Kentaro Senba, Noritaka Yamaguchi, Tadashi Yamamoto, Motoharu Seiki, Jun Ichiro Inoue

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Triple-negative breast cancers (TNBC), which include the basal-like and claudin-low disease subtypes, are aggressive malignancies for which effective therapeutic targets are lacking. NF-κB activation has an established role in breast malignancy, and it is higher in TNBC than other breast cancer subtypes. On this basis, we hypothesized that proteins derived from NF-κB target genes might be molecular targets for TNBC therapy. In this study, we conducted a microarray-based screen for novel NF-κB-inducible proteins as candidate therapeutic targets, identifying tropomodulin 1 (TMOD1) as a lead candidate. TMOD1 expression was regulated directly by NF-κB and was significantly higher in TNBC than other breast cancer subtypes. TMOD1 elevation is associated with enhanced tumor growth in a mouse tumor xenograft model and in a 3D type I collagen culture. TMOD1-dependent tumor growth was correlated with MMP13 induction, which was mediated by TMOD1-dependent accumulation of β-catenin. Overall, our study highlighted a novel TMOD1-mediated link between NF-κB activation and MMP13 induction, which accounts in part for the NF-κB-dependent malignant phenotype of TNBC.

    Original languageEnglish
    Pages (from-to)62-72
    Number of pages11
    JournalCancer Research
    Volume75
    Issue number1
    DOIs
    Publication statusPublished - 2015 Jan 1

    Fingerprint

    Tropomodulin
    Triple Negative Breast Neoplasms
    Breast Neoplasms
    Growth
    Neoplasms
    Catenins
    Collagen Type I
    Heterografts
    Breast
    Therapeutics
    Phenotype

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Ito-Kureha, T., Koshikawa, N., Yamamoto, M., Senba, K., Yamaguchi, N., Yamamoto, T., ... Inoue, J. I. (2015). Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth. Cancer Research, 75(1), 62-72. https://doi.org/10.1158/0008-5472.CAN-13-3455

    Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth. / Ito-Kureha, Taku; Koshikawa, Naohiko; Yamamoto, Mizuki; Senba, Kentaro; Yamaguchi, Noritaka; Yamamoto, Tadashi; Seiki, Motoharu; Inoue, Jun Ichiro.

    In: Cancer Research, Vol. 75, No. 1, 01.01.2015, p. 62-72.

    Research output: Contribution to journalArticle

    Ito-Kureha, T, Koshikawa, N, Yamamoto, M, Senba, K, Yamaguchi, N, Yamamoto, T, Seiki, M & Inoue, JI 2015, 'Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth', Cancer Research, vol. 75, no. 1, pp. 62-72. https://doi.org/10.1158/0008-5472.CAN-13-3455
    Ito-Kureha T, Koshikawa N, Yamamoto M, Senba K, Yamaguchi N, Yamamoto T et al. Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth. Cancer Research. 2015 Jan 1;75(1):62-72. https://doi.org/10.1158/0008-5472.CAN-13-3455
    Ito-Kureha, Taku ; Koshikawa, Naohiko ; Yamamoto, Mizuki ; Senba, Kentaro ; Yamaguchi, Noritaka ; Yamamoto, Tadashi ; Seiki, Motoharu ; Inoue, Jun Ichiro. / Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth. In: Cancer Research. 2015 ; Vol. 75, No. 1. pp. 62-72.
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