Panoply™ Human TYK2 Over-expressing Stable Cell Line

Synovial sarcoma (SS) is a rare soft tissue sarcoma characterized by high malignancy and poor prognosis. Preliminary studies suggest that evasion of apoptosis is a key factor in SS progression, primarily attributed to the overexpression of anti-apoptotic genes. However, the underlying mechanisms of this phenomenon remain incompletely understood. Here, researchers found that tyrosine kinase 2 (TYK2) is upregulated in highly malignant SS. Through in vitro and in vivo functional analyses, they confirmed that TYK2 significantly promotes the progression of SS cells. Mechanistically, TYK2 activates STAT3, which in turn promotes the expression of the anti-apoptotic gene BCL2. Inhibiting STAT3 activation with a specific inhibitor blocked TYK2-enhanced BCL2 expression, indicating that the TYK2/STAT3/BCL2 axis is a critical regulatory pathway mediating apoptosis evasion in SS cells. Furthermore, studies on the upstream regulatory mechanisms of TYK2 revealed that the fusion protein SS18-SSX enhances the transcriptional activity of the TYK2 gene by binding to its promoter region, thereby increasing its expression level. Therefore, the TYK2/STAT3/BCL2 axis is a key mechanism by which SS18-SSX mediates apoptosis evasion in SS cells. In summary, these findings contribute to understanding how SS18-SSX-driven TYK2 expression mediates apoptosis evasion mechanisms and suggest targeting TYK2 as a therapeutic strategy to induce apoptosis in SS cells.

Anti-apoptotic experiments showed that knockdown of TYK2 significantly increased the proportion of apoptotic cells in both SW982 and HS-SY-II cells (Figure 1A and C). Conversely, the proportion of apoptotic cells was significantly decreased in TYK2 overexpressing SW982 and HS-SY-II cell lines (Figure 1B and D), indicating that TYK2 is crucial for the anti-apoptotic process in SS cells. To further elucidate the effect of TYK2 on the apoptotic pathway, the expression levels of several apoptosis-related proteins were examined. The results showed that TYK2 knockdown significantly upregulated the levels of cleaved caspase-3 and cleaved PARP1 in both SW982 and HS-SY-II cells (Figure 1E and G), while the levels of cleaved caspase-3 and cleaved PARP1 were significantly downregulated in TYK2-overexpressing cells (Figure 1F and H). To further verify these results, researchers used flow cytometry to detect the proportion of cells labeled with cleaved caspase-3, which represents the degree of apoptosis. The data showed a significant increase in the proportion of cleaved caspase-3 in TYK2-knockdown SW982 and HS-SY-II cells. In summary, the TYK2-mediated cell apoptosis escape effect may be an important mechanism by which it promotes SS progression.

Figure 1. TYK2 drives anti-apoptosis in SS cells. (Qin W, et al., 2024)