biostudies-literatureUnknown12Parker KThe SS18-SSX fusion protein is an oncogenic driver in synovial sarcoma. At the molecular level, SS18-SSX functions as both an activator and a repressor to coordinate transcription of different genes responsible for tumorigenesis. Here, we identify the proto-oncogene <i>FYN</i> as a new SS18-SSX target gene and examine its relation to synovial sarcoma therapy. FYN is a tyrosine kinase that promotes cancer growth, metastasis and therapeutic resistance, but SS18-SSX appears to negatively regulate <i>FYN</i> expression in synovial sarcoma cells. Using both genetic and histone deacetylase inhibitor (HDACi)-based pharmacologic approaches, we show that suppression of SS18-SSX leads to <i>FYN</i> reactivation. In support of this notion, we find that blockade of FYN activity synergistically enhanceFrontiers in cell and developmental biology1422452https://www.ebi.ac.uk/biostudies/studies/S-EPMC11264242biostudies-literatureCombination of HDAC and FYN inhibitors in synovial sarcoma treatment.PMC11264242Anchondo GKondo TParker KZhang YSmith ASu LGuerrero Pacheco SfalseCombination of HDAC and FYN inhibitors in synovial sarcoma treatment.The SS18-SSX fusion protein is an oncogenic driver in synovial sarcoma. At the molecular level, SS18-SSX functions as both an activator and a repressor to coordinate transcription of different genes responsible for tumorigenesis. Here, we identify the proto-oncogene <i>FYN</i> as a new SS18-SSX target gene and examine its relation to synovial sarcoma therapy. FYN is a tyrosine kinase that promotes cancer growth, metastasis and therapeutic resistance, but SS18-SSX appears to negatively regulate <i>FYN</i> expression in synovial sarcoma cells. Using both genetic and histone deacetylase inhibitor (HDACi)-based pharmacologic approaches, we show that suppression of SS18-SSX leads to <i>FYN</i> reactivation. In support of this notion, we find that blockade of FYN activity synergistically enhance2024-01-01T00:00:00Z20242025-06-01T01:16:26.572Z2025-06-01T01:16:26.572ZS-EPMC112642423904545810.3389/fcell.2024.1422452