In an attempt to explain the high frequency of head and neck cancers in FA patients we have examined differences in the behaviour and signaling pathways of oral epithelial cells (cells that line the oral cavity) lacking Fanconi gene function. Experimental reduction of expression of FA-__A and FA-__C genes in oral epithelial cells results, as expected, in reduced growth, lower survival, and greater sensitivity to DNA damage. However, there is also a surprisingly wide and consistent range of further changes that do not appear to be explained as a direct consequence of lack of DNA repair. Two of the most interesting changes are (a) the greater tendency of such cells to enter an epithelial-__mesenchymal transition (EMT), producing cells that are more invasive and therapy resistant, and (b) reduced expression of Aldh enzymes that are associated with detoxification of aldehydes and function in normal cells to reduce DNA damage. This research will also help to discern why alcohol and other envronmental toxins increase cancer risk.
Researchers: Ian Mackenzie