論文

査読有り 国際誌
2019年7月

Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness.

Neoplasia (New York, N.Y.)
  • Youyi Chen
  • ,
  • I Wayan Sumardika
  • ,
  • Nahoko Tomonobu
  • ,
  • Rie Kinoshita
  • ,
  • Yusuke Inoue
  • ,
  • Hidekazu Iioka
  • ,
  • Yosuke Mitsui
  • ,
  • Ken Saito
  • ,
  • I Made Winarsa Ruma
  • ,
  • Hiroki Sato
  • ,
  • Akira Yamauchi
  • ,
  • Hitoshi Murata
  • ,
  • Ken-Ichi Yamamoto
  • ,
  • Shuta Tomida
  • ,
  • Kazuhiko Shien
  • ,
  • Hiromasa Yamamoto
  • ,
  • Junichi Soh
  • ,
  • Junichiro Futami
  • ,
  • Miyoko Kubo
  • ,
  • Endy Widya Putranto
  • ,
  • Takashi Murakami
  • ,
  • Ming Liu
  • ,
  • Toshihiko Hibino
  • ,
  • Masahiro Nishibori
  • ,
  • Eisaku Kondo
  • ,
  • Shinichi Toyooka
  • ,
  • Masakiyo Sakaguchi

21
7
開始ページ
627
終了ページ
640
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.neo.2019.04.006

Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes.

リンク情報
DOI
https://doi.org/10.1016/j.neo.2019.04.006
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31100639
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520639
ID情報
  • DOI : 10.1016/j.neo.2019.04.006
  • ISSN : 1522-8002
  • PubMed ID : 31100639
  • PubMed Central 記事ID : PMC6520639

エクスポート
BibTeX RIS