title: Senescent cells communicate via intercellular protein transfer.
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.
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Anat
authors: A
authors: Biran
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Meirav
authors: M
authors: Perelmutter
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Hilah
authors: H
authors: Gal
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Dominick G A
authors: DG
authors: Burton
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Yossi
authors: Y
authors: Ovadya
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Ezra
authors: E
authors: Vadai
authors: Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel.
authors: Tamar
authors: T
authors: Geiger
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; valery.krizhanovsky@weizmann.ac.il.
authors: Valery
authors: V
authors: Krizhanovsky
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D010179:Pancreas / Q000166:cytology* / Q000502:physiology; D058105:Polymerization; D021381:Protein Transport; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D020741:rho GTP-Binding Proteins
keywords: actin polymerization; cellular senescence; cytoplasmic bridges; natural killer cells