The Role of Sulfiredoxin in Tumorigenesis and Cancer Progression

Sulfiredoxin (Srx) is a novel gene that is highly expressed in several types of human tumors including cancers of skin and lung. However, the function of Srx in tumor development has not been well studied. The primary hypothesis of this study is that Srx has an oncogenic function that may contribute to tumorigenesis and cancer progression in human. The long-term goal of the project is to understand the function and molecular mechanisms of Srx in human cancer development and progression, which may provoke novel strategies for cancer prevention and treatment. The first aim of this study is to test whether genomic loss of Srx may cause mouse resistant to tumorigenesis in a chemical induced skin or colon carcinogenesis model (to be completed during the K99 phase). The second aim is to study the function and molecular basis of Srx in human lung cancer cell migration, invasion and metastasis. The third aim is to characterize proteins that interact with Srx and to determine how they contribute to the oncogenic function of Srx in human lung cancer cells. During the K99 phase, we have demonstrated the critical function of Srx in cancer development using methods including cell culture in vitro, mouse skin and colon carcinogenesis in vivo, and mouse models of human cancer cell tumorigenesis and metastasis, etc. In the R00 phase, the mechanistic study of Srx function will be focused on the cell signaling changes and protein-protein interactions using biochemistry and molecular biology techniques. The successful completion of the proposed research may further the understanding of the role of Srx in human cancer, broaden the knowledge of antioxidant proteins in tumorigenesis and cancer progression, and facilitate the development of novel strategies for cancer prevention and treatment.