Grant: Project Grant

Gastric cancer (GC) represents one of the leading causes of deaths caused by cancer worldwide. Although all included under the umbrella of GC, several subtypes of the disease have been described that differ based on their appearance and genetic make-up. Diffuse-type GC (DGC) represents a particularly aggressive form of the disease that is found with increasing frequency in recent years. DGC cells are known for harboring specific mutations that prevent them from forming junctions with other epithelial cells. Consequently, these tumors are highly invasive and can spread to neighboring tissues. Despite this understanding many of the underlying causes of DGC remain largely unknown. In general, a major contributing factor driving GC is chronic inflammation that often arises from certain bacterial infections. It is believed that inflammation disrupts the barrier formed by epithelial cells of the stomach and causing these to proliferate uncontrollably and form precancerous lesions, which have been hypothesized to initiate GC. However, the mechanisms underlying these transforming events again remain poorly understood. This proposal aims to address these key questions by investigating the roles of 2 important genes, Yap and Taz in regulating gastric regeneration, inflammation and DGC progression. Our proposal will develop novel mouse models of gastric cancer and primary cell cultures of the gastric epithelium to dissect the biological functions regulated by these genes using a range of state of the art molecular techniques.