RRC ID 56896
Author Takasugi M, Okada R, Takahashi A, Virya Chen D, Watanabe S, Hara E.
Title Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.
Journal 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.
Volume 8
Pages 15729
Published 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
Times Cited 82
Resource
Human and Animal Cells MCF7(RCB1904) OVK18(RCB1903)