2022 Fiscal Year Final Research Report
Role of SS18-SSX fusion oncoprotein in DNA repair
| Project/Area Number |
20K16312
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | DNA修復 / 滑膜肉腫 |
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| Outline of Final Research Achievements |
Synovial sarcoma is an aggressive tumor of adolescent and young adults characterized by the chromosomal translocation t(X;18)(p11.2;q11.2). This chromosomal translocation produces a chimeric oncoprotein SS18-SSX. SS18 is involved in epigenetic remodeling, transcription, and DNA replication, as a subunit of BAF complex, which is disrupted by the SS18-SSX chimeric protein. In this study, we sought to elucidate the mechanisms by which DNA repair is impaired in synovial sarcoma and synovial sarcoma cell lines are sensitized to DNA damaging agents. Using synovial sarcoma cell lines and several cancer cell lines stably expressing SS18-SSX, we found that RNF168 and RIF1 are essential for the survival of synovial sarcoma.
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| Free Research Field |
がん
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| Academic Significance and Societal Importance of the Research Achievements |
滑膜肉腫は悪性の軟部腫瘍であり、５年生存率は50~60%である。予後不良因子は、腫瘍径5cm以上、高悪性度である。転移がある場合、５年生存率は半減する。予後向上のためには再発や転移を抑制することが重要であり、術前術後の化学療法の充実が待たれる。我々の研究成果は悪性の軟部腫瘍である滑膜肉腫に対する化学療法の改良にも貢献しうるという社会的意義を有している。また、滑膜肉腫原因融合タンパク質SS18-SSXによるDNA修復およびDNA複製異常の解明という学術的意義も持ちうる。
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