The project will be entertaining the hypothesis that hypoxic environment can alter the activities of histone modifying enzymes that can influence cancer metastasis. Experiments will involve mostly biochemical analysis of proteins and gene expression.
The overall goal of this project is to investigate in detail how the KMTs (lysine methyltransferase) and the KDMs (lysine demethylase) are deregulated in cancer, and determining the effect of their deregulation on metastatic potential in breast cancer.
The hypotheses will be addressed through the following specific aims:
- To determine the relationship between tumour microenvironment (hypoxia) and the expression of the KMTs and the KDMs.
- To discover novel protein targets of the KMTs or the KDMs in breast cancer cells by protein complex purification assays combined with proteomic analysis. Identify and characterise proteins interacting with the KMTs (G9a, GLP, and EZH2) or the KDMs (JMJD1) in normal, non-metastatic and metastatic cancer cells.
- To determine the mechanism by which lysine methylation/demethylation of non-histone proteins affects gene expression and breast cancer metastasis.