RRC ID |
56896
|
著者 |
Takasugi M, Okada R, Takahashi A, Virya Chen D, Watanabe S, Hara E.
|
タイトル |
Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.
|
ジャーナル |
Nat Commun
|
Abstract |
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.
|
巻・号 |
8
|
ページ |
15729
|
公開日 |
2017-6-6
|
DOI |
10.1038/ncomms15728
|
PII |
ncomms15728
|
PMID |
28585531
|
PMC |
PMC5467215
|
MeSH |
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology*
Cell Line, Tumor
Cell Proliferation
Cellular Senescence
Ephrin-A2 / metabolism*
Female
Gene Expression Regulation, Neoplastic
Humans
MCF-7 Cells
Mass Spectrometry
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology*
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Reactive Oxygen Species / metabolism
Receptor, EphA2
Recombinant Proteins / metabolism
Signal Transduction
|
IF |
11.878
|
引用数 |
82
|
リソース情報 |
ヒト・動物細胞 |
MCF7(RCB1904)
OVK18(RCB1903) |