論文

査読有り 国際誌
2018年2月1日

Novel YAP1 Activator, Identified by Transcription-Based Functional Screen, Limits Multiple Myeloma Growth

Molecular Cancer Research
  • Junichi Maruyama
  • Kazutoshi Inami
  • Fumiyoshi Michishita
  • Xinliang Jiang
  • Hiroaki Iwasa
  • Kentaro Nakagawa
  • Mari Ishigami-Yuasa
  • Hiroyuki Kagechika
  • Norio Miyamura
  • Jun Hirayama
  • Hiroshi Nishina
  • Daichi Nogawa
  • Kouhei Yamamoto
  • Yutaka Hata
  • 全て表示

16
2
開始ページ
197
終了ページ
211
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/1541-7786.MCR-17-0382
出版者・発行元
American Association for Cancer Research Inc.

Yes-associated protein 1 (YAP1) interacts with numerous transcription factors, including TEA-domain family proteins (TEAD) and p73. YAP1 is negatively regulated by the tumor suppressor Hippo pathway. In human cancers, the deregulation of the Hippo pathway and YAP1 gene amplification lead to the activation of YAP1, which induces epithelial–mesenchymal transition (EMT) and drug resistance. YAP1 inhibitors are expected to be useful in cancer therapy. On the other hand, in certain cancers, YAP1 upregulates p73-dependent gene transcription and behaves as a tumor suppressor. Moreover, as YAP1 regulates self-renewal and differentiation of tissue stem cells and plays an important role in tissue homeostasis, YAP1 activators may contribute to the regenerative medicine. With this in our mind, we screened for YAP1 activators by using human retinal pigment epithelial ARPE-19 cells expressing the TEAD-responsive fluorescence reporter under the coexpression of YAP1. From an extensive chemical compound library (n ¼ 18,606) 47 candidate YAP1 activators were identified. These compounds were characterized to determine whether this assay provides bona fide YAP1 activators. Importantly, one YAP1 activator was effective against the human multiple myeloma IM-9 cells and chronic myeloid leukemia K562 cells. Implications: YAP1 activation limits growth, induces apoptosis, and may be useful at suppressing hematological cancers.

リンク情報
DOI
https://doi.org/10.1158/1541-7786.MCR-17-0382
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29061667
ID情報
  • DOI : 10.1158/1541-7786.MCR-17-0382
  • ISSN : 1557-3125
  • ISSN : 1541-7786
  • PubMed ID : 29061667
  • SCOPUS ID : 85041489220

エクスポート
BibTeX RIS