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Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells

Author

Listed:
  • Nanase Igarashi

    (Cancer Institute, Japanese Foundation for Cancer Research
    Tokyo Medical and Dental University)

  • Kenichi Miyata

    (Cancer Institute, Japanese Foundation for Cancer Research
    Japanese Foundation for Cancer Research)

  • Tze Mun Loo

    (Cancer Institute, Japanese Foundation for Cancer Research)

  • Masatomo Chiba

    (Cancer Institute, Japanese Foundation for Cancer Research)

  • Aki Hanyu

    (Cancer Institute, Japanese Foundation for Cancer Research)

  • Mika Nishio

    (Cancer Institute, Japanese Foundation for Cancer Research)

  • Hiroko Kawasaki

    (Cancer Institute, Japanese Foundation for Cancer Research)

  • Hao Zheng

    (Nagoya University Graduate School of Medicine)

  • Shinya Toyokuni

    (Nagoya University Graduate School of Medicine)

  • Shunsuke Kon

    (Tokyo University of Science)

  • Keiji Moriyama

    (Tokyo Medical and Dental University)

  • Yasuyuki Fujita

    (Kyoto University)

  • Akiko Takahashi

    (Cancer Institute, Japanese Foundation for Cancer Research
    Japanese Foundation for Cancer Research
    Japan Agency for Medical Research and Development (AMED))

Abstract

Cellular senescence and cell competition are important tumor suppression mechanisms that restrain cells with oncogenic mutations at the initial stage of cancer development. However, the link between cellular senescence and cell competition remains unclear. Senescent cells accumulated during the in vivo aging process contribute toward age-related cancers via the development of senescence-associated secretory phenotype (SASP). Here, we report that hepatocyte growth factor (HGF), a SASP factor, inhibits apical extrusion and promotes basal protrusion of Ras-mutated cells in the cell competition assay. Additionally, cellular senescence induced by a high-fat diet promotes the survival of cells with oncogenic mutations, whereas crizotinib, an inhibitor of HGF signaling, provokes the removal of mutated cells from mouse livers and intestines. Our study provides evidence that cellular senescence inhibits cell competition-mediated elimination of oncogenic cells through HGF signaling, suggesting that it may lead to cancer incidence during aging.

Suggested Citation

  • Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31642-4
    DOI: 10.1038/s41467-022-31642-4
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