SS18-SSX-Dependent YAP/TAZ Signaling in Synovial Sarcoma复制标题

滑膜肉瘤中YAP/TAZ信号SS18-SSX-Dependent

Synovial sarcoma (SySa) is an aggressive malignancy comprising approximately 2% of all sarcomas with a predominance in adolescents and young adults. Wide surgical resection, radiotherapy and chemotherapy with ifosfamide and doxorubicin represent established therapeutic options; however, prognosis in the metastatic situation is poor. Specific molecularly targeted therapeutic approaches are currently limited.The molecular hallmark of SySa is a pathognomonic reciprocal t(X;18) (p11; q11) translocation, leading to the fusion of SS18 (SYT) and one of the homologues SSX genes (most frequently SSX1 or SSX2, in rare cases SSX4), generating chimeric SS18-SSX fusion proteins. Although the SS18-SSX protein is known to play a crucial role in SySa tumorigenesis, its specific biological function and its mechanism of action remain to be elucidated. Neither SS18 and the SSX proteins, nor the chimeric SS18-SSX oncoproteins feature known DNA-binding motifs; however, they have been reported to contribute to the dysregulation of gene expression through association with SWI/SNF and Polycomb chromatin remodeling complexes.

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