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

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

Research output: Contribution to journalArticle

14 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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ito-Kureha, T., Koshikawa, N., Yamamoto, M., Semba, K., Yamaguchi, N., Yamamoto, T., Seiki, M., & 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