論文

査読有り
2015年7月

JNK signaling is converted from anti- to pro-tumor pathway by Ras-mediated switch of Warts activity

DEVELOPMENTAL BIOLOGY
  • Masato Enomoto
  • ,
  • Daisuke Kizawa
  • ,
  • Shizue Ohsawa
  • ,
  • Tatsushi Igaki

403
2
開始ページ
162
終了ページ
171
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ydbio.2015.05.001
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

The c-Jun N-terminal kinase (JNK) pathway is a dual-functional oncogenic signaling that exerts both anti- and pro-tumor activities. However, the mechanism by which JNK switches its oncogenic roles depending on different cellular contexts has been elusive. Here, using the Drosophila genetics, we show that hyperactive Ras acts as a signaling switch that converts JNK's role from anti- to pro-tumor signaling through the regulation of Hippo signaling activity. In the normal epithelium, JNK signaling antagonizes the Hippo pathway effector Yorkie (Yki) through elevation of Warts activity, thereby suppressing tissue growth. In contrast, in the presence of hyperactive Ras, JNK signaling enhances Yki activation by accumulating F-actin through the activity of the LIM domain protein Ajuba, thereby promoting tissue growth. We also find that the epidermal growth factor receptor (EGFR) signaling uses this Ras-mediated conversion of JNK signaling to promote tissue growth. Our observations suggest that Ras-mediated switch of the JNK pathway from anti- to pro-tumor signaling could play crucial roles in tumorigenesis as well as in normal development. (C) 2015 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 38

リンク情報
DOI
https://doi.org/10.1016/j.ydbio.2015.05.001
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25967126
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000356839600005&DestApp=WOS_CPL

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