論文

2017年2月

The ligand Sas and its receptor PTP1OD drive tumour-suppressive cell competition

NATURE
  • Masatoshi Yamamoto
  • ,
  • Shizue Ohsawa
  • ,
  • Kei Kunimasa
  • ,
  • Tatsushi Igaki

542
7640
開始ページ
246
終了ページ
250
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/nature21033
出版者・発行元
NATURE PUBLISHING GROUP

Normal epithelial cells often exert anti-tumour effects against nearby oncogenic cells. In the Drosophila imaginal epithelium, clones of oncogenic cells with loss-of-function mutations in the apico-basal polarity genes scribble or discs large are actively eliminated by cell competition when surrounded by wild-type cells'. Although c-Jun N-terminal kinase (JNK) signalling plays a crucial role in this cell elimination(1-5), the initial event, which occurs at the interface between normal cells and polarity-deficient cells, has not previously been identified. Here, through a genetic screen in Drosophila, we identify the ligand Sas and the receptor-type tyrosine phosphatase PTP10D as the cell-surface ligand-receptor system that drives tumour-suppressive cell competition. At the interface between the wild-type 'winner' and the polarity-deficient 'loser' clones, winner cells relocalize Sas to the lateral cell surface, whereas loser cells relocalize PTP10D there. This leads to the trans activation of Sas-PTP10D signalling in loser cells, which restrains EGFR signalling and thereby enables elevated JNK signalling in loser cells, triggering cell elimination. In the absence of Sas-PTP10D, elevated EGFR signalling in loser cells switches the role of JNK from pro-apoptotic to pro-proliferative by inactivating the Hippo pathway, thereby driving the overgrowth of polarity-deficient cells. These findings uncover the mechanism by which normal epithelial cells recognize oncogenic polarity-deficient neighbours to drive cell competition.

Web of Science ® 被引用回数 : 48

リンク情報
DOI
https://doi.org/10.1038/nature21033
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000393737500044&DestApp=WOS_CPL