Grant: Project Grant

The MICAL1 enzyme produces the reactive oxygen species molecule H2O2, and is expressed at higher than normal levels in a variety of cancer types, including breast, liver, kidney, pancreas, skin and brain/central nervous system cancers. To determine how MICAL1 contributes to cancer, we blocked its expression and observed significant effects on protein oxidation, cell migration, survival and tumour growth in a mouse breast cancer model. Together, these observations reveal a major role of MICAL1 in cancer, indicating that MICAL1 is a potential cancer drug target due to its role as a critically important signalling linker. Building on our experience and knowledge of signal transduction pathways in cancer, particularly in examining how protein oxidation influences cancer cell motility, we will determine how the MICAL1 protein contributes to cancer growth via targeted protein oxidation. We hypothesize that: (1) MICAL1 responds to upstream signals by changing its specific activity, leading to the oxidation of target proteins to affect their functions; (2) MICAL1-induced protein oxidations contribute to cancer growth, invasion and metastasis; (3) MICAL1 is a novel potential cancer drug target. By characterizing how MICAL1-induced protein oxidation affects cellular functions, we will address a significant knowledge gap regarding protein oxidation as a fundamentally important protein modification. These studies will uncover fundamental new knowledge about the role of regulated and targeted protein oxidation in signal transduction pathways, and will determine whether MICAL1 is a critically important signal transduction intermediary, and thus a novel cancer drug target.