WWOX as a Signal Mediator in Pediatric Osteosarcoma
Cancer is one of the leading causes of death in human diseases. The main hypothesis underlying causes of human cancer suggests that important genes responsible for cell growth and survival are affected thus leading cells to grow without control. One important type of genes implicated in cancer development is called tumor suppressor genes (TSGs). Once affected (usually deleted or mutated), TSGs cause cells to undergo cellular changes leading to tumor formation. We recently reported that the WWOX gene is an important TSG. We generated a mouse that lacks the Wwox gene expression and found that mice develop a wide spectrum of tumors suggesting that absence of Wwox enhances tumor development. One striking finding was the development of bone tumors, called osteosarcoma. Osteosarcoma is the most common type of bone cancer, and the sixth most common type of cancer in children. In this proposal we are planning to characterize the tumor suppressor function of the WWOX gene in osteosrcoma cells. In addition, we plan to identify the molecular mechanism in which WWOX participates. Finally, we propose to further investigate an important cross-talk between WWOX and an important bone cancer gene called RUNX2. The proposed work addresses an unanswered question in bone cancer medical research and may ultimately provide us with important insights into the role of Wwox signaling pathway in the regulation of bone cell growth and carcinogenesis. These results will further suggest whether WWOX and members of its signaling pathway may be targets for therapeutic intervention in human bone tumors.