論文

査読有り
2020年2月20日

MMP24 as a Target of YAP Is a Potential Prognostic Factor in Cancer Patients

Bioengineering
  • Wataru Sugimoto
  • ,
  • Katsuhiko Itoh
  • ,
  • Hiroaki Hirata
  • ,
  • Yoshinori Abe
  • ,
  • Takeru Torii
  • ,
  • Yasumasa Mitsui
  • ,
  • Yemima Budirahardja
  • ,
  • Nobuyuki Tanaka
  • ,
  • Keiko Kawauchi

7
1
開始ページ
18
終了ページ
18
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/bioengineering7010018
出版者・発行元
MDPI AG

The extracellular matrix (ECM) surrounding cancer cells becomes stiffer during tumor progression, which influences cancer cell behaviors such as invasion and proliferation through modulation of gene expression as well as remodeling of the actin cytoskeleton. In this study, we show that MMP24 encoding matrix metalloproteinase (MMP)-24 is a novel target gene of Yes-associated protein (YAP), a transcription coactivator known as a mechanotransducer. We first examined the effect of substrate stiffness on MMP24 expression in MCF-7 human breast cancer cells and showed that the expression of MMP24 was significantly higher in cells grown on stiff substrates than that on soft substrates. The MMP24 expression was significantly reduced by knockdown of YAP. In contrast, the expression of constitutively active YAP increased MMP24 promoter activity. In addition, binding of YAP to the MMP24 promoter was confirmed by the chromatin immunoprecipitation (ChIP) assay. These results show that ECM stiffening promotes YAP activation, thereby inducing MMP24 expression. Based on the Human Protein Atlas database, breast cancer patients with lower MMP24 expression exhibit the worse survival rates overall. Thus, MMP24 may negatively regulate the aggressiveness of cancer cells under the stiff ECM environment during tumor progression.

リンク情報
DOI
https://doi.org/10.3390/bioengineering7010018
URL
https://www.mdpi.com/2306-5354/7/1/18/pdf
ID情報
  • DOI : 10.3390/bioengineering7010018
  • eISSN : 2306-5354
  • ORCIDのPut Code : 69537396

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