News Releases & Research Results Elucidation of cancer-inhibiting effect of cellular senescence at the level of organism, with a perspective of development of new cancer therapy utilizing cell senescence mechanism

Results of research led by the study group including Assistant Professor Shingo Komura of Department of Orthopaedics, Gifu University Graduate School of Medicine (then, Center for iPS Cell Research and Application, Kyoto University) and Appointed Researcher Kenji Ito and Professor Yasuhiro Yamada of Institute of Medical Science, University of Tokyo.

• Induced pluripotent stem (iPS) cells derived from the cell line of clear cell sarcoma ^*1 (CCS-IPSCs) were used to successfully generate chimeric mice ^*2 with the same genetic mutations identical to those in cells of clear cell sarcoma as a cancer
  *1: Clear Cell Sarcoma (CCS): A tumor that preferentially arises in soft tissue such as the skin and extremities. It frequently occurs in the third and fourth decades.
  *2: Artificial generated mice that have genetically different cells derived from transplants and host embryo.
• Precise assessment of tissues from generated chimeric mice showed that tumor was not formed in most tissues despite the presence of genetic mutations and that cellular senescence was associated with tumor formation suppression in the chimeric mice.
• It was demonstrated that not only genetic mutations but also cell/tissue-dependent epigenomic signatures ^*3 also play an important role for carcinogenesis at the level of organism.
  *3: Collective information that regulates genetic function without modifying DNA base sequence.

This research and development were supported by Advanced Research and Development Programs for Medical Innovation (AMED-CREST).

The research and development results were published on September 5 in Nature Communications.

Komura S., et al. Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas, Nature Communications
DOI：10.1038/s41467-019-11745-1