2. Academic Validation
  3. Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells

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

  • Nat Commun. 2022 Jul 18;13(1):4157. doi: 10.1038/s41467-022-31642-4.
Nanase Igarashi  # 1 2,  Kenichi Miyata  # 1 3,  Tze Mun Loo  # 1,  Masatomo Chiba 1,  Aki Hanyu 1,  Mika Nishio 1,  Hiroko Kawasaki 1,  Hao Zheng 4,  Shinya Toyokuni 4,  Shunsuke Kon 5,  Keiji Moriyama 2,  Yasuyuki Fujita 6,  Akiko Takahashi 7 8 9
Affiliations

Affiliations

  • 1 Project for Cellular Senescence, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 2 Department of Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, Japan.
  • 3 Cancer Cell Communication Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 4 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • 5 Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
  • 6 Department of Molecular Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 7 Project for Cellular Senescence, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. [email protected].
  • 8 Cancer Cell Communication Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan. [email protected].
  • 9 Advanced Research & Development Programs for Medical Innovation (PRIME), Japan Agency for Medical Research and Development (AMED), Tokyo, Japan. [email protected].
  • # Contributed equally.
PMID: 35851277 DOI: 10.1038/s41467-022-31642-4
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.

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