論文

査読有り 本文へのリンクあり
2017年12月1日

ASK1 facilitates tumor metastasis through phosphorylation of an ADP receptor P2Y 12 in platelets

Cell Death and Differentiation
  • Miki Kamiyama
  • ,
  • Toshiaki Shirai
  • ,
  • Shogo Tamura
  • ,
  • Katsue Suzuki-Inoue
  • ,
  • Shogo Ehata
  • ,
  • Kei Takahashi
  • ,
  • Kohei Miyazono
  • ,
  • Yoshihiro Hayakawa
  • ,
  • Takehiro Sato
  • ,
  • Kohsuke Takeda
  • ,
  • Isao Naguro
  • ,
  • Hidenori Ichijo

24
12
開始ページ
2066
終了ページ
2076
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/cdd.2017.114
出版者・発行元
NATURE PUBLISHING GROUP

Tumor metastasis is the major cause of deaths in cancer patients and is modulated by intertwined stress-responsive signaling cascades. Here we demonstrate that deletion of stress-responsive apoptosis signal-regulating kinase 1 (Ask1) in platelets results in unstable hemostasis and drastic attenuation of tumor lung metastasis, both of which are attributable to platelet dysfunction. Platelet-specific deletion of Ask1 in mice leads to defects in ADP-dependent platelet aggregation, unstable hemostasis and subsequent attenuation of tumor metastasis. We also revealed that activating phosphorylation of Akt is attenuated in Ask1-deficient platelets, contrary to the previous reports suggesting that Akt is negatively regulated by ASK1. Mechanistically, ASK1-JNK/p38 axis phosphorylates an ADP receptor P2Y 12 at Thr345, which is required for the ADP-dependent sustained Akt activity that is vital to normal platelet functions. Our findings offer insight into positive regulation of Akt signaling through P2Y 12 phosphorylation as well as MAPK signaling in platelets by ASK1 and suggest that ASK1-JNK/p38 axis provides a new therapeutic opportunity for tumor metastasis.

Web of Science ® 被引用回数 : 24

リンク情報
DOI
https://doi.org/10.1038/cdd.2017.114
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28753204
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000414963300008&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85034073125&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85034073125&origin=inward
ID情報
  • DOI : 10.1038/cdd.2017.114
  • ISSN : 1350-9047
  • eISSN : 1476-5403
  • PubMed ID : 28753204
  • SCOPUS ID : 85034073125
  • Web of Science ID : WOS:000414963300008

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