Challenge for elucidation of cross talk between cellular senescence and cell competition

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22571
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Takahashi Akiko 公益財団法人がん研究会, がん研究所 細胞老化プロジェクト, プロジェクトリーダー (60380052)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 細胞老化 / 細胞競合 / がん抑制 / SASP

Outline of Final Research Achievements

Both cellular senescence and cell competition caused by oncogenic stimuli induce apical elimination or irreversible cell cycle arrest of oncogenic cells, thereby acting as an important tumor suppression mechanism in the earliest stages of cancer development. In contrast, senescent cells accumulated during the aging process in vivo secrete many inflammatory proteins. This phenomenon, termed the senescence-associated secretory phenotype (SASP), contributes to age-related cancers. Although both cellular senescence and cell competition are induced by oncogenic stressors, the relationship between them remains unclear. Here we show that one SASP factor inhibits apical extrusion of mutated cells. In addition, cellular senescence results in survival of mutated cells, whereas the inhibitor clearly causes the elimination of those cells from mouse livers. Our data provides the first evidence that cellular senescence inhibits cell competition-induced elimination of oncogenic cells.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

老化細胞が分泌するSASP因子による、もう一つのがん抑制機構である細胞競合の抑制という生命現象は、現在までに全く報告のない新規のがん制御機構であり、本研究成果は腫瘍生物学における新しいコンセプトの創成となった。
さらに、将来的に細胞競合や細胞老化といったがん抑制機構を標的とした治療戦略を立てる上で重要な知見を提供し、今後SASPを制御することで細胞競合をも制御できる可能性に繋がり、臨床的な応用研究に発展する可能性が高い。