Konstantinos V Floros, Carter K Fairchild, Jinxiu Li, Kun Zhang, Jane L Roberts, Richard Kurupi, Bin Hu, Vita Kraskauskiene, Nayyerehsadat Hosseini, Shanwei Shen, Melissa M Inge, Kylie Smith-Fry, Li Li, Afroditi Sotiriou, Krista M Dalton, Asha Jose, Elsamani I Abdelfadiel, Yanli Xing, Ronald D Hill, Jamie M Slaughter, Mayuri Shende, Madelyn R Lorenz, Mandy R Hinojosa, Benjamin R Belvin, Zhao Lai, Sosipatros A Boikos, Angeliki M Stamatouli, Janina P Lewis, Masoud H Manjili, Kristoffer Valerie, Renfeng Li, Ana Banito, Andrew Poklepovic, Jennifer E Koblinski, Trevor Siggers, Mikhail G Dozmorov, Kevin B Jones, Senthil K Radhakrishnan, Anthony C Faber
Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981...
April 27, 2024: bioRxiv