The two other promising targets identified from this RNAi screen were STK10 and TNK2. Our results clearly showed that both these genes are involved in Ewings sarcoma cell growth and survival and are anti apoptotic. These results suggest that both STK10 and TNK2 would be promising kinase targets for therapeutic intervention in Ewings sarcoma. Recently, several studies by Grueneberg and colleagues selleck products have shown that various different types of cancer cells depend on different and specific kinases for cell survival. They successfully studied kinomes in cervical, lung and renal cells. On browsing their target gene lists we did not see STK10 and TNK2 as hits in any of their screens, which also points to the fact that these two Inhibitors,Modulators,Libraries tar gets might be specific to Ewings sarcoma.

Mining of gene expression data indicate that both STK10 and TNK2 are not highly over expressed in Ewings sarcoma, hence over expression of these genes may not be a driver for their functional specificity in this disease. STK10 belongs to the Ste20 family of serine/threonine kinases plays an important role in numerous cellular functions such as growth, apoptosis, and morphogenesis. This Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries protein has not been associated with cancer and most of the previous Inhibitors,Modulators,Libraries reports have studied its expression in T cells, lymphocytes and hematopoetic tissues. STK10 is a human homo log of murine Lok, a serine/threonine kinase highly Inhibitors,Modulators,Libraries expressed in lymphocytes.

STK10 can associate with PLK1 in cells and can phosphorylate PLK1 in vitro and engineered NIH 3T3 cell lines that over express a dominant negative version of STK10 display an altered cell cycle phenotype characterized by increased DNA content, which raises the possibility that expression selleck chem Axitinib of a dominant negative STK10 may impinge upon PLK1 function in vivo and it has previously been shown that unregulated expression of PLK1 can result in a variety of nuclear defects. These observations are in accordance with our data, wherein we show that STK10 knockdown leads to increased apoptosis and cell death of Ewings sarcoma cells. Our results also show that the normal fibroblast cells do not depend on STK10, as there is minimal cell death after STK10 knockdown in these cells. Although, there have been no previous reports dis cussing the role of STK10 in sarcomas, our results clearly demonstrate an important role for STK10 in growth and survival of Ewings sarcoma cells. Next, we validated the results for TNK2 knockdown and similar to STK10, TNK2 also led to increased cell death and apoptosis. TNK2, also known as ACK1 binds specifically to Cdc42. Cdc42, like other Rho family members, is involved in transducing oncogenic signals from Ras to develop a transformation phenotype in mammalian cells.