Location: Children's Nutrition Research CenterTitle: Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-kB signaling Author
Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/2010
Publication Date: 1/4/2011
Citation: Qu, Y., Wang, J., Ray, P.S., Guo, H., Huang, P., Shin-Sim, M., Bukoye, B.A., Liu, B., Lee, A.V., Lin, X., Huang, P., Martens, J.W., Giuliano, A.E., Zhang, N., Ning-Hui, C., Cui, X. 2011. Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-kB signaling. Journal of Clinical Investigation. 121(1):212-225. Interpretive Summary: People like to consume a diet supplemented with antioxidants to ensure that they maintain their health and prevent disease. This study demonstrated that one type of antioxidant protein, called TXNL2, helps protect human breast cancer cells from high levels of free radicals. Furthermore, changing TXNL2 proteins in cancer cells can destroy tumor growth and development. Therefore, these findings suggest that TXNL2 could be a new therapeutic target for the treatment of breast cancer.
Technical Abstract: Cancer cells have an efficient antioxidant system to counteract their increased generation of ROS. However, whether this ability to survive high levels of ROS has an important role in the growth and metastasis of tumors is not well understood. Here, we demonstrate that the redox protein thioredoxin-like 2 (TXNL2) regulates the growth and metastasis of human breast cancer cells through a redox signaling mechanism. TXNL2 was found to be overexpressed in human cancers including breast cancers. Knockdown of TXNL2 in human breast cancer cell lines increased ROS levels and reduced NF-'B activity, resulting in inhibition of in vitro proliferation, survival, and invasion. In addition, TXNL2 knockdown inhibited tumorigenesis and metastasis of these cells upon transplantation into immunodeficient mice. Furthermore, analysis of primary breast cancer samples demonstrated that enhanced TXNL2 expression correlated with metastasis to the lung and brain and with decreased overall patient survival. Our studies provided insight into redox-based mechanisms underlying tumor growth and metastasis, and suggest that TXNL2 could be a target for treatment of breast cancer.