Senescent cells communicate via intercellular protein transfer

Anat Biran, Meirav Perelmutter, Hilah Gal, Dominick G.A. Burton, Yossi Ovadya, Ezra Vadai, Tamar Geiger, Valery Krizhanovsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mammalian cells mostly rely on extracellular molecules to transfer signals to other cells. However, in stress conditions, more robust mechanisms might be necessary to facilitate cell–cell communications. Cellular senescence, a stress response associated with permanent exit from the cell cycle and the development of an immunogenic phenotype, limits both tumorigenesis and tissue damage. Paradoxically, the long-term presence of senescent cells can promote tissue damage and aging within their microenvironment. Soluble factors secreted from senescent cells mediate some of these cell-nonautonomous effects. However, it is unknown whether senescent cells impact neighboring cells by other mechanisms. Here we show that senescent cells directly transfer proteins to neighboring cells and that this process facilitates immune surveillance of senescent cells by natural killer (NK) cells. We found that transfer of proteins to NK and T cells is increased in the murine preneoplastic pancreas, a site where senescent cells are present in vivo. Proteomic analysis and functional studies of the transferred proteins revealed that the transfer is strictly dependent on cell–cell contact and CDC42-regulated actin polymerization and is mediated at least partially by cytoplasmic bridges. These findings reveal a novel mode of intercellular communication by which senescent cells regulate their immune surveillance and might impact tumorigenesis and tissue aging.

Original languageEnglish
Pages (from-to)791-802
Number of pages12
JournalGenes and Development
Volume29
Issue number8
DOIs
StatePublished - 2014

Keywords

  • Actin polymerization
  • Cellular senescence
  • Cytoplasmic bridges
  • Natural killer cells

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