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Cancer Res. 2015 Jan 1;75(1):62-72. doi: 10.1158/0008-5472.CAN-13-3455. Epub 2014 Nov 14.

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

Author information

1
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. Cell Signal Unit, Okinawa Institute of Science and Technology, Okinawa, Japan.
2
Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
3
Department of Life Science and Medical Bio-science, Waseda University, Tokyo, Japan.
4
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
5
Cell Signal Unit, Okinawa Institute of Science and Technology, Okinawa, Japan.
6
Graduate School of Medicine, Kochi University, Kochi, Japan.
7
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. jun-i@ims.u-tokyo.ac.jp.

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.

PMID:
25398440
DOI:
10.1158/0008-5472.CAN-13-3455
[Indexed for MEDLINE]
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