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

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 and Akiko Takahashi ()
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Nanase Igarashi: Cancer Institute, Japanese Foundation for Cancer Research
Kenichi Miyata: Cancer Institute, 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

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31642-4

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