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Synovial sarcoma (SS) is a malignant soft tissue lesion and most commonly arises in young adults. Chromosomal translocation t(X;18)(p11;q11) results in the formation of SS18 / SSX by gene fusion of the SS18 gene on chromosome 18 to either SSX1 , SSX2 , or SSX4 gene located on chromosome X, which is detected in more than 95% of SSs. Although multiple lines of evidence suggest that the SS18/SSX fusion is the oncogene in this tumor, the protein expression profiles associated with SS18 / SSX have yet to be elucidated. In this study, we conducted proteomic studies using SS18 / SSX knockdown in three SS cell lines to identify the regulated proteins associated with SS18/SSX in SS. Isobaric tags for relative and absolute quantitation (i-TRAQ) analyses identified approximate 1700-2,000 proteins regulated by the SS18/SSX fusion in each SS cell line. We also analyzed the three profiles to identify proteins that were similarly altered in all 3 cell lines and found 17 consistently upregulated and 18 consistently downregulated proteins, including TAGLN and ACTN4. In addition, network analyses identified several critical pathways including RUNX2 and SMARCA4. RUNX2 and SMARCA4 had the highest ranking in these identified pathways. In addition, we found that expression of TAGLN inhibited cell viability in SS cell lines. Our data suggest that the differentiation and cell growth of SS may be enhanced by the identified proteins induced by SS18/SSX. We believe that the findings obtained in the present functional analyses will help to improve our understanding of the relationship between SS18/SSX and malignant behavior in SS.

Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma