論文

査読有り 国際誌
2017年6月6日

Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.

Nature communications
  • Masaki Takasugi
  • ,
  • Ryo Okada
  • ,
  • Akiko Takahashi
  • ,
  • David Virya Chen
  • ,
  • Sugiko Watanabe
  • ,
  • Eiji Hara

8
開始ページ
15729
終了ページ
15729
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/ncomms15728

Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. However, the altered secretome of senescent cells can promote the growth of the surrounding cancer cells. Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role in the function of senescent cell secretome has been largely unexplored. Here, we show that exosome-like small EVs (sEVs) are important mediators of the pro-tumorigenic function of senescent cells. sEV-associated EphA2 secreted from senescent cells binds to ephrin-A1, that is, highly expressed in several types of cancer cells and promotes cell proliferation through EphA2/ephrin-A1 reverse signalling. sEV sorting of EphA2 is increased in senescent cells because of its enhanced phosphorylation resulting from oxidative inactivation of PTP1B phosphatase. Our results demonstrate a novel mechanism of reactive oxygen species (ROS)-regulated cargo sorting into sEVs, which is critical for the potentially deleterious growth-promoting effect of the senescent cell secretome.

リンク情報
DOI
https://doi.org/10.1038/ncomms15728
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28585531
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467215
ID情報
  • DOI : 10.1038/ncomms15728
  • PubMed ID : 28585531
  • PubMed Central 記事ID : PMC5467215

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